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Results for “randomised trial”

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At least 127 records · Page 7Linked to original sources

PubMed2002

A randomised trial of population screening for melanoma.

OBJECTIVES: Melanoma is a significant cause of morbidity and mortality worldwide and incidence is increasing. Survival after treatment is inversely related to the thickness of the tumour at diagnosis. Population screening has the potential to reduce mortality but there is no conclusive evidence of benefit. Such evidence can come best from a randomised trial. Here we describe the design of a community based randomised trial of a population screening programme for melanoma in Queensland, Australia and early results of the first phase of the trial. METHODS: A total of 44 communities (aggregate population 560 000 adults aged 30 years or more) will be randomised to receive either a community based screening programme for 3 years or normal practice. The screening programme promotes thorough skin self examination and whole body skin examination by a doctor and provides open access skin cancer screening clinics. In its first phase, the trial is underway in nine intervention and nine control communities. The primary outcome measure is mortality from melanoma during 15 years of follow up. RESULTS: The first phase of the trial has shown the feasibility of implementing a population skin screening programme including regular skin cancer screening clinics, and has shown the strong support of communities and doctors for the programme. There has been a significant 2.5-fold increase in participation in screening in the intervention communities in this first phase after the first 12 months of the trial and no significant increase in participation in screening in control communities during this period. CONCLUSIONS: The design of a community based randomised trial of screening for melanoma has been successfully peer reviewed and the intervention has been shown to be feasible in practice. This randomised trial may be one of the last opportunities to develop the evidence required for public health recommendations for population screening for melanoma.

Humans↗

PubMed1989

Cerebral palsy among children born during the Dublin randomised trial of intrapartum monitoring.

In a randomised trial involving 13,079 liveborn children intrapartum care by electronic fetal heart rate monitoring, with scalp blood sampling when indicated, was associated with a 55% reduction in neonatal seizures. Reassessment, when aged 4, of the 9 children in the intensively monitored group and 21 in the control group who survived after neonatal seizures showed that 3 such children in each group had cerebral palsy. A fourth child in the intensively monitored group with cerebral palsy had had transient abnormal neurological signs during the neonatal period. 8 other children in the intensively monitored group and 7 in the control group who had not had abnormal neurological signs in the neonatal period also had cerebral palsy. 16 (78%) of the total of 22 cases of cerebral palsy had not shown clinical signs suggestive of intrapartum asphyxia. Thus, compared with intermittent intrapartum monitoring, intensive monitoring has little, if any, protective effect against cerebral palsy.

Asphyxia Neonatorum↗

PubMed1982

Colloidal bismuth subcitrate tablets and placebo in chronic duodenal ulceration: a double-blind, randomised trial.

In a double-blind, randomised trial of 46 outpatients with endoscopically proven chronic duodenal ulceration, 22 were given colloidal bismuth subcitrate (De-Nol, Gist-Brocades) and 24 were given placebo for four weeks. Clinical and laboratory assessment was made after two and four weeks' therapy. Endoscopic healing was demonstrated in 86.5% of patients taking colloidal bismuth tablets and in 25% of patients taking placebo. We observed no clinical or biochemical side effects in either group. These results indicate that colloidal bismuth subcitrate tablets are well tolerated, and are effective in healing chronic duodenal ulcers.

Adult↗

PubMed2026

Strategies to improve recruitment to randomised trials.

BACKGROUND: Recruiting participants to randomised controlled trials (RCTs) is challenging. Identifying effective recruitment strategies would benefit health research: poor recruitment leads to underpowered trials, reducing the reliability of findings and increasing the risk of wasted resources, ethical concerns, and trial failure. Evidence to inform recruitment strategies is increasingly generated through Studies Within A Trial (SWATs), which are methodological studies embedded within host RCTs. This is an update of a review last published in 2018. OBJECTIVES: Primary: to quantify the effects of strategies to improve recruitment of participants to RCTs. Secondary: to evaluate recruitment strategies' cost-effectiveness and impact on retention, and the equity, diversity, and inclusion (EDI) characteristics of recruited participants. SEARCH METHODS: We used MEDLINE, Embase, and six other databases to identify the studies included in the review. We also sought unpublished recruitment SWATs through social media and targeted email dissemination to trial methodology networks. The latest search date was 16 February 2023. SELECTION CRITERIA: We included randomised SWATs evaluating trial recruitment strategies embedded in healthcare and non-healthcare trials. We excluded quasi-randomised, hypothetical, questionnaire-only, retention-only, or clinician incentive studies. DATA COLLECTION AND ANALYSIS: Primary outcome: proportion of eligible participants or centres recruited. SECONDARY OUTCOMES: cost-effectiveness, retention rates, and EDI characteristics of included participants. We conducted random-effects meta-analysis for strategies evaluated in at least two studies; otherwise, we synthesised results narratively. We reported effects as risk differences (RDs) with 95% confidence intervals (CIs), and assessed between-trial heterogeneity. We used GRADE to assess the certainty of evidence for the primary outcome. We expressed cost-effectiveness as the incremental cost per additional participant recruited in pounds sterling (GBP). MAIN RESULTS: We identified 91 eligible studies (53 new to this update), providing 94 comparisons and involving at least 176,747 participants. Eighty-one studies involved strategies aimed at trial participants, while 10 evaluated strategies aimed at recruiters. All were healthcare studies. We found 65 recruitment strategies; 49 were evaluated in a single study. Only five strategies were supported by high-certainty evidence according to GRADE criteria, and we focus on these strategies in the summary below. Open-label trials versus blinded, placebo trials. Open-label trials recruited more participants than blinded trials (RD 10%, 95% CI 8% to 12%; 3 studies, 9004 participants), corresponding to approximately 10 additional participants per 100 approached. The studies involved mostly women in the UK and Estonia. No cost or retention data were reported. Telephone reminder versus no telephone reminder. Telephone reminders to people who did not respond to an initial postal invitation boosted recruitment by 6% (95% CI 3% to 9%; 2 studies, 1450 participants), in trials with low underlying recruitment (we are less certain for trials with over 10% recruitment). The studies involved people with a mean age of 58 years in Canada and Norway. No cost or retention data were reported. Recruitment primer letter versus no letter. Pre-recruitment letters and leaflets designed to encourage participation made little or no difference to recruitment (absolute improvement 1%, 95% CI -1% to 2%; 2 studies, 5376 participants), and were associated with increased costs compared to not sending a primer (incremental cost: GBP 2.08). The studies involved mostly older white people in the UK and Ireland. Multimedia information via a digital link/QR code plus paper participant information leaflet (PIL) versus paper PIL alone. This made little or no difference to recruitment (absolute improvement 0%, 95% CI -1% to 1%; 7 studies, 11,612 participants) and retention (absolute improvement 0%, 95% CI -2% to 3%; 5 studies, 7403 participants), and increased costs compared to not including multimedia information (incremental cost: GBP 0.78). The studies involved people in the UK. Optimised, user-tested PIL versus standard PIL. Optimising participant information leaflets (e.g. through user-testing the leaflet with the target population to shape its content, format, and appearance) made little or no difference to recruitment: absolute improvement was 0% (95% CI 0% to 1%; 6 studies, 27,805 participants). The studies involved people in the UK. Only one study reported EDI data; participants were mostly older women. No cost or retention data were reported. We had moderate-certainty evidence for 13 other strategies; confidence was often reduced because the results came from single studies. Seven strategies involved changes to how potential participants received information; four involved changes to trial conduct; one targeted the recruiter or recruitment site; and one tested non-monetary incentives. We had much less confidence in the other 47 comparisons because the studies had design flaws, were single studies, or had very uncertain results. Costs were reported in only 17 of 91 studies. Strategy impact on retention was reported in 15 studies. All but one study (99%) were from high-income countries. The most reported demographics were age (49 studies), sex (32 studies), gender (27 studies), and education level (16 studies). AUTHORS' CONCLUSIONS: The evidence on strategies to improve trial recruitment remains broad but lacks depth. Of 65 strategies evaluated, only five were supported by high-certainty evidence. Open-label trial designs and telephone reminders to non-responders increased recruitment, while optimised participant information leaflets, recruitment primer letters, and multimedia information provided alongside a paper participant information leaflet had little or no effect. Reporting of participant characteristics was poor, limiting assessment of equity, diversity, and inclusion across most studies. Evidence is heavily skewed toward high-income countries. Future research must prioritise evaluations in low-to-middle-income settings and consistently report cost, retention, and EDI outcomes. We strongly urge the methodology research community to strengthen the evidence base by prioritising replications of existing strategies over the development and testing of new ones. FUNDING: National Institute for Health and Care Research (Advanced Fellowship, Adwoa Parker, reference:NIHR302256). Health Research Board, Republic of Ireland, Evidence Synthesis Ireland (grant ESI-2021-001) REGISTRATION: This review updates an earlier Cochrane review, which was first published in 2002 and subsequently updated in 2007, 2010, and 2018. Previous versions of the review and their protocols are available at: https://doi.org/10.1002/14651858.MR000013.pub2 https://doi.org/10.1002/14651858.MR000013.pub3 https://doi.org/10.1002/14651858.MR000013.pub4 https://doi.org/10.1002/14651858.MR000013.pub5 https://doi.org/10.1002/14651858.MR000013.pub6.

Randomized Controlled Trials as Topic↗

PubMed1994

Antibiotic prophylaxis in permanent pacemaker implantation: a prospective randomised trial.

BACKGROUND: Pacemaker pocket infection is a potentially serious problem after permanent pacemaker implantation. Antibiotic prophylaxis is commonly prescribed to reduce the incidence of this complication, but current trial evidence of its efficacy is conflicting. A large prospective randomised trial was therefore performed of antibiotic prophylaxis in permanent pacemaker implantation. The intention was firstly to determine whether antibiotic prophylaxis is efficacious in these patients and secondly to identify which patients are at the highest risk of infection. METHODS: A prospective randomised open trial of flucloxacillin (clindamycin if the patient was allergic to penicillin) v no antibiotic was performed in a cohort of patients undergoing first implantation of a permanent pacing system over a 17 month period. Intravenous antibiotics were started at the time of implantation and continued for 48 hours. The trial endpoint was a repeat operation for an infective complication. RESULTS: 473 patients were entered into a randomised trial. 224 received antibiotic prophylaxis and 249 received no antibiotics. A further 183 patients were not randomised but were treated according to the operator's preference (64 antibiotics, 119 no antibiotics); these patients are included only in the analysis of predictors of infection. Patients were followed up for a mean (SD) of 19(5) months. Among the patients in the randomised group there were nine infections requiring a repeat operation, all in the group not receiving antibiotic (P = 0.003). In the total patient cohort there were 13 infections, all but one in the non-antibiotic group (P = 0.006). Nine of the infections presented as erosion of the pulse generator or electrode, three as septicaemia secondary to Staphylococcus aureus, and one as a pocket abscess secondary to Staphylococcus epidermidis. Infections were significantly more common when the operator was inexperienced (< or = 100 previous patients), the operation was prolonged, or after a repeat operation for non-infective complications (principally lead displacement). Infection was not significantly more common in patients identified preoperatively as being at high risk (for example patients with diabetes mellitus, patients receiving long term steroid treatment), although there was a trend in this direction. CONCLUSIONS: Antibiotic prophylaxis significantly reduced the incidence of infective complications requiring a repeat operation after permanent pacemaker implantation. It is suggested that antibiotics should be used routinely.

Aged↗

PubMed2002

"Why don't they just tell me straight, why allocate it?" The struggle to make sense of participating in a randomised controlled trial.

Randomised controlled trials are the acknowledged 'gold standard' method of evaluating the effectiveness of treatments, but little is known about how and why patients decide to participate in trials nor how much they understand about trial design. In this study, in-depth, semi-structured interviews were carried out with 33 middle aged and older men with lower urinary tract symptoms related to benign prostatic disease, 22 of whom had consented to participate and 11 refused to take part in a randomised trial. The trial was evaluating the effectiveness of a new technology (laser therapy) compared with standard surgery (transurethral resection of the prostate ) and conservative management (monitoring without active intervention) (the CLasP study). Purposive sampling was used to include participants from different centres, each treatment arm, and at different stages in participation, as well as those indicated to have refused participation. Interviews explored their recall and understanding of trial information, and their reasoning about how they were allocated to a treatment. Data were analysed thematically according to the methods of constant comparison, and by examining each participant's narrative of their experiences. Most participants recalled major aspects of trial design, including the involvement of chance, but the case studies showed that most also held other co-existing (and sometimes contradictory) views about their treatment allocation. The key to understanding their experiences was their engagement in a struggle to understand the trial in the context of their own beliefs, their recall of the study information and their actual experiences of the trial. The outcome of the struggle was the placing of trust in clinicians or the development of distrust. Non-participants made sense of their experiences in similar ways, but gave different reasons for non-participation than indicated by recruiters. This study shows that most eligible patients, whatever their level of knowledge, will struggle to make sense of their participation in randomised trials. The provision of clearer written information or time to discuss the trial with particular individuals might be beneficial, although greater public understanding of trials is also needed.

Aged↗

PubMed1992

The role of prophylactic antibiotics in caesarean section--a randomised trial.

A prospective randomised controlled study was conducted over a 6 month period on the value of administering prophylactic antibiotics in patients undergoing emergency caesarean section at the Ipoh General Hospital. A total of 222 patients were randomised to receive 24 hours of ampicillin (500 mg per dose), cefoperazone (1 gm per dose) or no antibiotics. In all parameters of patient morbidity, the group receiving cefoperazone showed significantly better results as compared to the group not receiving antibiotics. The ampicillin group also had favourable results but generally not achieving statistical significance. Prophylactic antibiotics appear to be beneficial and consideration should be given to make it a routine in all emergency caesarean sections.

Ampicillin↗

PubMed1994

Feasibility study of a randomised trial of ovarian cancer screening.

OBJECTIVES: To assess the feasibility of a randomised trial of ovarian cancer screening by vaginal ultrasonography. SETTING: A population based study, recruiting a random sample of the female population aged 46 to 65 years living in Copenhagen, Denmark. DESIGN: Randomised controlled trial allocating 50% to the study group having vaginal ultrasonography, and 50% to the control group having no examination. (a) Acceptability of the study was evaluated by the proportion of eligible women willing to participate in the study. (b) The false positive rate was evaluated as the proportion of women without ovarian cancer referred for an operation because of abnormal ovaries detected by ultrasonography. RESULTS: 950 (64.3%) of the 1477 eligible women participated in the study. At the first scan abnormal ovaries were detected in 54 of 435 women (12%), significantly more frequently among younger women. Nine women were referred for an operation because of abnormal findings in the ovaries, giving a false positive rate of 2%. Ovarian size and morphology found at operation corresponded with those at ultrasonography; none of them was malignant. CONCLUSIONS: A randomised controlled trial of ovarian cancer screening using vaginal ultrasonography seems acceptable in the general population. The rate of abnormal ovaries at ultrasonography with the cut offs used in this study was quite high. Such a study is, therefore, feasible, but it is proposed that it is carried out in an older age group (50-64 years) and that the cut offs used for ovarian size and morphology are re-evaluated. Second line tests, such as colour Doppler flow, should be considered in order to reduce the false positive rate.

Aged↗

PubMed2003

Can randomised trials rely on existing electronic data? A feasibility study to explore the value of routine data in health technology assessment.

OBJECTIVES: To estimate the feasibility, utility and resource implications of electronically captured routine data for health technology assessment by randomised controlled trials (RCTs), and to recommend how routinely collected data could be made more effective for this purpose. DATA SOURCES: Four health technology assessments that involved patients under care at five district general hospitals in the UK using four conditions from distinct classical specialties: inflammatory bowel disease, obstructive sleep apnoea, female urinary incontinence, and total knee replacement. Patient-identifiable, electronically stored routine data were sought from the administration and clinical database to provide the routine data. REVIEW METHODS: Four RCTs were replicated using routine data in place of the data already collected for the specific purpose of the assessments. This was done by modelling the research process from conception to final writing up and substituting routine for designed data activities at appropriate points. This allowed a direct comparison to be made of the costs and outcomes of the two approaches to health technology assessment. The trial designs were a two-centre randomised trial of outpatient follow-up; a single-centre randomised trial of two investigation techniques; a three-centre randomised trial of two surgical operations; and a single-centre randomised trial of perioperative anaesthetic intervention. RESULTS: Generally two-thirds of the research questions posed by health technology assessment through RCTs could be answered using routinely collected data. Where these questions required analysis of NHS resource use, data could usually be identified. Clinical effectiveness could also be judged, using proxy measures for quality of life, provided clinical symptoms and signs were collected in sufficient detail. Patient and professional preferences could not be identified from routine data but could be collected routinely by adapting existing instruments. Routine data were found potentially to be cheaper to extract and analyse than designed data, and they also facilitate recruitment as well as have the potential to identify patient outcomes captured in remote systems that may be missed in designed data collection. The study confirmed previous evidence that the validity of routinely collected data is suspect, particularly in systems that are not under clinical and professional control. Potential difficulties were also found in identifying, accessing and extracting data, as well as in the lack of uniformity in data structures, coding systems and definitions. CONCLUSIONS: Routine data have the potential to support health technology assessment by RCTs. The cost of data collection and analysis is likely to fall, although further work is required to improve the validity of routine data, particularly in central returns. Better knowledge of the capability of local systems and access to the data held on them is also essential. Routinely captured clinical data have real potential to measure patient outcomes, particularly if the detail and precision of the data could be improved.

Arthroplasty, Replacement, Knee↗

PubMed1996

A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial.

We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4.0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-18.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to palliative treatment of advanced cancer. However, in this trial there was no significant benefit in toxicity or other aspects of quality of life.

Adult↗

PubMed2006

A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial.

BACKGROUND: Long-term data from randomised trials on the consequences of treatment with a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or both are lacking. Here, we report results from the FIRST trial, which compared initial treatment strategies for clinical, immunological, and virological outcomes. METHODS: Between 1999 and 2002, 1397 antiretroviral-treatment-naive patients, presenting at 18 clinical trial units with 80 research sites in the USA, were randomly assigned in a ratio of 1:1:1 to a protease inhibitor (PI) strategy (PI plus nucleoside reverse transcriptase inhibitor [NRTI]; n=470), a non-nucleoside reverse transcriptase inhibitor (NNRTI) strategy (NNRTI plus NRTI; n=463), or a three-class strategy (PI plus NNRTI plus NRTI; n=464). Primary endpoints were a composite of an AIDS-defining event, death, or CD4 cell count decline to less than 200 cells per mm3 for the PI versus NNRTI comparison, and average change in CD4 cell count at or after 32 months for the three-class versus combined two-class comparison. Analyses were by intention-to-treat. This study is registered ClinicalTrials.gov, number NCT00000922. FINDINGS: 1397 patients were assessed for the composite endpoint. A total of 388 participants developed the composite endpoint, 302 developed AIDS or died, and 188 died. NNRTI versus PI hazard ratios (HRs) for the composite endpoint, for AIDS or death, for death, and for virological failure were 1.02 (95% CI 0.79-1.31), 1.07 (0.80-1.41), 0.95 (0.66-1.37), and 0.66 (0.56-0.78), respectively. 1196 patients were assessed for the three-class versus combined two-class primary endpoint. Mean change in CD4 cell count at or after 32 months was +234 cells per mm3 and +227 cells per mm3 for the three-class and the combined two-class strategies (p=0.62), respectively. HRs (three-class vs combined two-class) for AIDS or death and virological failure were 1.15 (0.91-1.45) and 0.87 (0.75-1.00), respectively. HRs (three-class vs combined two-class) for AIDS or death were similar for participants with baseline CD4 cell counts of 200 cells per mm3 or less and of more than 200 cells per mm3 (p=0.38 for interaction), and for participants with baseline HIV RNA concentrations less than 100 000 copies per mL and 100,000 copies per mL or more (p=0.26 for interaction). Participants assigned the three-class strategy were significantly more likely to discontinue treatment because of toxic effects than were those assigned to the two-class strategies (HR 1.58; p<0.0001). INTERPRETATION: Initial treatment with either an NNRTI-based regimen or a PI-based regimen, but not both together, is a good strategy for long-term antiretroviral management in treatment-naive patients with HIV.

Adult↗

PubMed1980

Early intravenous atenolol treatment in suspected acute myocardial infarction. Preliminary report of a randomised trial.

214 patients were studied in a randomised trial to determine whether administraiton of intravenous atenolol within 12 hours of chest pain reduced eventual infarct size, as estimated by cumulative enzyme release and by ECG changes. 135 patients already had ECG evidence of infarction at entry; 72 received atenolol which significantly decreased subsequent enzyme release (atenolol and control means = 121 IU, SE +/- 10 and 177 IU, SE +/- 17; 2p < 0.005) and enhanced R-wave preservation (atenolol and control means = 46% +/- 3 and 36% +/- 3; 2p < 0.02). 79 patients had no evidence of infarction at entry; 44 did not receive atenolol and 27 of these subsequently developed infarction, whereas only 11 of 35 treated patients infarcted during their hospital stay (2p < 0.01). In hospital, fewer atenolol patients died (4 vs 9), had non-fatal cardiac arrests (2 vs 6), or required therapy for heart-failure (36 vs 47). Unlike many previous trials which had negative results, in this trial we gave the drug intravenously and promptly (median of 4 hours from onset of pain to injecton), thereby achieving early beta-blockade.

Acute Disease↗

PubMed1996

Patient preferences in randomised trials: threat or opportunity?

OBJECTIVES: To assess whether it is feasible to elicit patients' preferences for treatments and then to proceed with randomisation which may allocate those with preferences to their less preferred treatment; and to describe which prognostic variables were associated with such preferences within the context of a randomised trial of an exercise programme for back pain. METHODS: The first 97 patients enrolled in a randomised controlled trial (RCT) for the treatment of back pain were asked about their preferences, health characteristics and other prognostic variables. RESULTS: Fifty-eight (60%) patients preferred to be allocated to the exercise programme whilst 38 (39%) were indifferent; one patient preferred conventional general practitioner (GP) management. No patient refused randomisation. Comparing patients preferring the exercise programme with indifferent patients showed that the former had a higher belief in the effectiveness of the new treatment (P < 0.01), tended to have worse back pain (P = 0.09), had back pain for a shorter duration (P = 0.04), and tended to have had more GP home visits (P = 0.06). CONCLUSIONS: For many randomised trials preference may be an important prognostic variable. In such circumstances, preference should be taken into account in the final analysis. This study demonstrates it is sometimes feasible to randomise patients to their less preferred treatment, thus allowing more robust statistical comparisons between randomised groups. This modification may make RCTs more rigorous and improve their external validity.

Adult↗

PubMed2004

The eVALuate study: two parallel randomised trials, one comparing laparoscopic with abdominal hysterectomy, the other comparing laparoscopic with vaginal hysterectomy.

OBJECTIVE: To compare the effects of laparoscopic hysterectomy and abdominal hysterectomy in the abdominal trial, and laparoscopic hysterectomy and vaginal hysterectomy in the vaginal trial. DESIGN: Two parallel, multicentre, randomised trials. SETTING: 28 UK centres and two South African centres. PARTICIPANTS: 1380 women were recruited; 1346 had surgery; 937 were followed up at one year. Primary outcome Rate of major complications. RESULTS: In the abdominal trial laparoscopic hysterectomy was associated with a higher rate of major complications than abdominal hysterectomy (11.1% v 6.2%, P = 0.02; difference 4.9%, 95% confidence interval 0.9% to 9.1%) and the number needed to treat to harm was 20. Laparoscopic hysterectomy also took longer to perform (84 minutes v 50 minutes) but was less painful (visual analogue scale 3.51 v 3.88, P = 0.01) and resulted in a shorter stay in hospital after the operation (3 days v 4 days). Six weeks after the operation, laparoscopic hysterectomy was associated with less pain and better quality of life than abdominal hysterectomy (SF-12, body image scale, and sexual activity questionnaires). In the vaginal trial we found no evidence of a difference in major complication rates between laparoscopic hysterectomy and vaginal hysterectomy (9.8% v 9.5%, P = 0.92; difference 0.3%, -5.2% to 5.8%), and the number needed to treat to harm was 333. We found no evidence of other differences between laparoscopic hysterectomy and vaginal hysterectomy except that laparoscopic hysterectomy took longer to perform (72 minutes v 39 minutes) and was associated with a higher rate of detecting unexpected pathology (16.4% v 4.8%, P = < 0.01). However, this trial was underpowered. CONCLUSIONS: Laparoscopic hysterectomy was associated with a significantly higher rate of major complications than abdominal hysterectomy. It also took longer to perform but was associated with less pain, quicker recovery, and better short term quality of life. The trial comparing vaginal hysterectomy with laparoscopic hysterectomy was underpowered and is inconclusive on the rate of major complications; however, vaginal hysterectomy took less time.

Adult↗

PubMed2000

Important issues in planning and conducting multi-centre randomised trials in cancer and publishing their results.

The principles and practical issues involved in planning and conducting multi-centre randomised trials in cancer and in publishing their results are reviewed for the benefit of those conducting trials or planning to do so. There is increasing public awareness of the importance of randomised trials and this needs to be nurtured. Questions addressed by trials must be clinically worthwhile, and trials must be planned and conducted to provide reliable results that will convince the clinical community and influence future clinical practice to patients' benefit. Trial protocols must justify the trial and give clear and unambiguous instructions to collaborating centres. Only data necessary for answering the trial questions should be collected, and the reliability of data should be checked. All trials should be published in peer-reviewed journals, and ways should be considered of communicating their results to patients, their families and the public. Wide consultation and independent review are needed to achieve these aims.

Clinical Protocols↗

PubMed2004

A randomised trial of accelerated radiotherapy for localised invasive bladder cancer.

BACKGROUND AND PURPOSE: To evaluate the efficacy and toxicity of an accelerated fractionation regimen to treat localised muscle invasive bladder cancer. PATIENTS AND METHODS: A prospective randomised trial was undertaken in 229 patients randomised between 1988 and 1998 comparing accelerated fractionation (AF) to a dose of 60.8 Gy in 32 fractions over 26 days with conventional fractionation (CF) treating to 64 Gy in 32 fractions over 45 days. Accelerated fractionation was delivered using two fractions per day with a 6h gap between fractions and with the first daily fraction size being 1.8 Gy and the second daily fraction size being 2.0 Gy. There was a 1 week treatment gap after the first 12 fractions. Conventional fractionation was one fraction per day, 5 days per week. Eligible patients had clinical stage T2 or T3, N0 or N1, M0 transitional cell carcinoma. The primary endpoint of the trial was local control and the trial was powered to detect a 20% difference (alpha 0.05, power 90%). Secondary endpoints were toxicity and survival. RESULTS: In the initial phase of the trial, randomisation was unequal such that in total 129 patients were randomised to accelerated fractionation and 100 to conventional fractionation. Acute toxicity was evaluable in 121 patients treated with AF and 96 patients treated with CF. RTOG grade 2 or 3 bowel toxicity was noted in 44% of AF patients compared to 26% of CF patients (P trend =0.001). Acute grade 2 or 3 bladder toxicity was seen in 35% of AF patients compared to 36% of CF patients (P=0.99). Late radiation toxicity was evaluated in patients surviving free from local recurrence at 2 years post treatment. Late radiation toxicity equivalent to RTOG grade 2 or more had occurred in 44% (95% CI 34-55%) of AF patients and in 38% (95% CI 26-49%) of CF patients (logrank over 5 years follow-up P=0.23). There was no significant difference in analysis of time to loss of local tumour control comparing the two treatment arms; local recurrence was recorded in 29 of the 100 patients treated with CF and in 41 of 129 patients treated with AF (logrank P=0.86). There was also no significant difference between the treatment arms comparing disease-free survival and overall survival. The overall survival figures at 3 years were for AF 54% (95% CI 45-63%) and for CF 47% (95% CI 36-57%). By 5 years the overall survival was 37% for AF and 40% for CF. There were two treatment related deaths, both on the AF arm of the trial. CONCLUSIONS: This accelerated fractionation schedule did not improve on the efficacy of conventional fractionation for patients with T2 and T3 bladder cancer and accelerated fractionation was associated with increased acute bowel reactions.

Adult↗

PubMed2004

Carotid artery stenting:the need for randomised trials.

Endovascular treatment for carotid artery stenosis avoids some of the complications of carotid endarterectomy, but has not been widely accepted. Concerns about the risks and benefits of endovascular treatment led to the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). There was no difference in major outcome events between endovascular treatment and carotid endarterectomy, but the rate of procedural stroke or death was higher than desirable. There was no difference either in the rate of stroke during follow-up, but the confidence intervals were very wide and severe ipsilateral carotid stenosis was more frequent 1 year after endovascular treatment than after carotid surgery. Two other randomised trials of carotid stenting were stopped early after poor outcomes in stented patients. These early trials used techniques which have now been superseded, but the results emphasise the need to improve the safety of endovascular treatment. Recent advances designed to improve safety include new designs of stents and delivery systems, and devices designed to protect the brain from embolisation during stenting. However, there is little convincing evidence that these new devices reduce the rate of stroke. Moreover, a systematic review of the existing randomised trial data concluded that there the current evidence does not support a shift away from recommending carotid endarterectomy as the standard treatment for carotid stenosis. There is therefore a clear need for further randomised trials of carotid stenting. Three of the ongoing trials, EVA-3S, SPACE and ICSS (CAVATAS-2), have prospectively agreed to combine individual patient data after completion of follow-up. This meta-analysis will provide results similar to a mega-trial and should also allow informative subgroup analyses. The co-operation between the trials in agreeing to perform this meta-analysis is a major advance in trial design. The result should determine whether carotid stenting truly rivals carotid endarterectomy as the treatment of choice for carotid stenosis.

Carotid Stenosis↗

PubMed1991

Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomised trials.

OBJECTIVE: To investigate the effect of intravenous magnesium on mortality in suspected acute myocardial infarction. DESIGN: Systematic overview of all available randomised trials in which patients were allocated to receive either intravenous magnesium or otherwise similar treatment without magnesium. SETTING: Coronary care units of several hospitals. PATIENTS: 1301 patients in seven randomised trials. MAIN OUTCOME MEASURE: Short term mortality. RESULTS: Considering the seven trials collectively there were 25 (3.8%) deaths among 657 patients allocated to receive magnesium and 53 (8.2%) deaths among 644 patients allocated control, generally during hospital follow up. This represents a 55% reduction in the odds of death (p less than 0.001) with 95% confidence intervals ranging from about one third to about two thirds. 70 of 648 patients allocated magnesium compared with 109 of 641 controls had serious ventricular arrhythmias, suggesting that magnesium reduces the incidence, though the definition varied among trials. Other adverse effects were rare in the limited number of patients for whom this data were available. CONCLUSION: Despite the limited number of patients randomised this overview suggests that intravenous magnesium therapy may reduce mortality in patients with acute myocardial infarction. Further large scale trials to confirm (or refute) these findings are desirable.

Hospitalization↗