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Results for “phase 3”

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At least 73 records · Page 4Linked to original sources

PubMed2006

Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study.

OBJECTIVE: The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal lysosomal storage disease with no effective treatment. STUDY DESIGN: Thirty-nine patients with MPS VI were evaluated in a randomized, double-blind, placebo-controlled, multicenter, multinational study for 24 weeks. The primary efficacy variable was the distance walked in a 12-minute walk test (12MWT), whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion. All patients received drug in an open-label extension period for an additional 24 weeks. RESULTS: After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001). Infusions were generally safe and well tolerated. Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein. CONCLUSION: rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile.

Adolescent↗

PubMed1995

[Phase 3 multicenter clinical study of 111In-DTPA-D-octreotide (MP-1727) in patients with gastrointestinal hormone producing tumors].

A phase 3 multicenter clinical study was performed to investigate the efficacy, safety and usefulness of MP-1727, a novel tumor imaging agent which binds to somatostatin receptors, in 23 patients with gastrointestinal hormone producing tumor. The efficacy was graded effective or very effective in 16 cases (76.2%) out of 21 cases who could be evaluated. Positive predictive accuracy was 77.8% (7/9) for carcinoids, 100% (5/5) for gastrinomas and 40.0% (2/5) for insulinomas. In three cases, tumor lesions which had been unknown were detected by MP-1727 scintigraphy. The consistent ratio between scintigraphically positive sites and preinjection localizations was 82.0% (41/50 sites) in total. Although adverse drug reactions were observed in two cases, the safety was graded 'not problematic at all' in all of 23 cases. These results show that MP-1727 is a very useful radiopharmaceutical for detection and localization of gastrointestinal hormone producing tumors.

Adult↗

PubMed2003

Week 48 resistance surveillance in two phase 3 clinical studies of adefovir dipivoxil for chronic hepatitis B.

Seven hundred nucleoside treatment-naive patients were enrolled in two phase 3 trials of adefovir dipivoxil (ADV) for the treatment of chronic hepatitis B. To monitor for the emergence of potential adefovir resistance mutations over the first 48 weeks, all intent-to-treat patients (467 ADV-treated and 228 placebo patients) were included in a prospectively defined, treatment-blinded, virology substudy. The study protocol mandated genotypic analysis for all patients with detectable hepatitis B virus (HBV) DNA by Roche Amplicor polymerase chain reaction (PCR) at baseline and week 48, and in vitro phenotypic analyses for patients with conserved site substitutions in HBV polymerase or 1.0 log(10) or greater increase in HBV DNA from nadir. Paired sequences of the entire HBV reverse transcriptase were obtained for 271 ADV-treated and 227 placebo patients by using a sequencing method that detects down to 30% of minor species present within mixtures. Four substitutions (rtS119A, rtH133L, rtV214A, and rtH234Q) developed once each at conserved sites in HBV polymerase in 4 ADV-treated patients. Seven conserved site substitutions developed in 6 placebo patients. HBV mutants encoding the 4 substitutions that emerged in ADV-treated patients remained fully susceptible to adefovir in vitro. Furthermore, these 4 ADV-treated patients had HBV-DNA reductions of 3.3 to 5.9 log(10) copies/mL by week 48 with no rebound. All other substitutions occurred at very low frequencies (<1.6%) at polymorphic sites and were not associated with HBV-DNA increases in patients or adefovir resistance in vitro. In conclusion, no adefovir resistance mutations were identified in a large group of chronic hepatitis B patients treated with ADV for 48 weeks.

Adenine↗

PubMed2000

Determination of Water-Oil Interfacial Area during 3-Phase Gravity Drainage in Porous Media.

Water-oil interfacial area in porous media was determined in laboratory experiments using sand columns consisting of either 2 (water and oil) or 3 (water, oil, and air) fluid phases. Surfactant sorption at the water-oil interface was directly measured for a wide range of water, oil, and air saturations undergoing gravity drainage. Differing values of the water-oil interfacial tension were also examined. The Gibbs adsorption equation was then used to obtain values for the water-oil interfacial area. Both 2- and 3-phase water-oil experiments showed a linear increase in interfacial area with decreasing water saturation. Results also showed that interfacial areas were not affected by changes in interfacial tension. The interfacial areas in the 3-phase experiments were less than half the calculated values of the corresponding 2-phase experiments, which contradicts predictions from a conventional pore level analysis of 3-phase flow. Copyright 2000 Academic Press.

Journal Article↗

PubMed2026

Efficacy and Safety of a Single-Pill Triple Combination of Valsartan, Amlodipine, and Chlorthalidone in Patients With Essential Hypertension Inadequately Controlled on Dual Therapy With Valsartan and Amlodipine: A Randomized, Double-Blind, Multicenter, Phase 3 Trial.

Many hypertensive patients require three or more antihypertensive agents to achieve target blood pressure. This randomized, double-blind, multicenter phase 3 trial conducted in South Korea evaluated the efficacy and safety of a single-pill triple combination therapy with valsartan (Val), amlodipine (Aml), and chlorthalidone (CTD) in patients whose blood pressure remained inadequately controlled on Val/Aml dual therapy. Patients uncontrolled after 4 weeks of Val/Aml 80/5 mg were randomized 1:1 to either Val/Aml/CTD 80/5/12.5 mg or Val/Aml 80/5 mg using a double-dummy design. After 2 weeks, doses were escalated to Val/Aml/CTD 160/5/25 mg or Val/Aml 160/5 mg, respectively, for a total treatment duration of 6 weeks. The primary endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Of 193 randomized patients, 178 completed the study. The least squares mean ± SE change in MSSBP was -19.70 ± 1.31 mmHg in the Val/Aml/CTD group versus -8.71 ± 1.26 mmHg in the control group, yielding a statistically significant between-group difference of -10.99 ± 1.81 mmHg (95% CI, -14.56 to -7.41; p < 0.0001). No serious adverse events occurred in the Val/Aml/CTD group, compared with an incidence of 1.98% in the control group (p = 0.4985). Triple combination therapy with Val/Aml/CTD demonstrated superior blood pressure reduction and a favorable safety profile in patients with essential hypertension inadequately controlled on Val/Aml dual therapy, supporting its use as an effective treatment option in this population. Trial Registration: This trial was prospectively registered at ClinicalTrials.gov (identifier: NCT06416865).

Humans↗

PubMed1994

[Phase 3 clinical study of 99mTc-MAG3 injectable, a dynamic renal imaging agent--comparison with 123I-OIH and 99mTc-DTPA].

A Phase 3 clinical study of 99mTc-mercaptoacetyl glycylglycylglycine (99mTc-MAG3) injectable was performed in 506 patients with renal and/or urinary disorders. The scintigraphic findings and renogram patterns of 99mTc-MAG3 were similar to those of 123I-OIH, and Tmax and T1/2 of the 99mTc-MAG3 renogram correlated with those of 123I-OIH (r = 0.62 and r = 0.74, respectively). The clinical efficacy of 99mTc-MAG3, evaluated by the investigators in the same patients, was superior to the efficacy of 123I-OIH and 99mTc-DTPA in 93 of 150 patients (62.0%) and 68 of 151 patients (45%), respectively. The image quality and the reliability of the scintigraphic findings with 99mTc-MAG3 were superior to those with 123I-OIH and 99mTc-DTPA, which reflect the more abundant photons of 99mTc-MAG3 than those of 123I-OIH and higher renal extraction of 99mTc-MAG3 than those of 99mTc-DTPA, respectively. Neither adverse reactions nor abnormal laboratory findings due to 99mTc-MAG3 administration were observed. These results suggest that 99mTc-MAG3 injectable is safe and a useful radiopharmaceutical for diagnosis of renal and urinary disorders.

Adult↗

PubMed2001

[A randomized, double-blind, placebo-controlled, phase 3 trial comparing SMS 201-995 pa LAR plus tamoxifen versus tamoxifen plus placebo in women with locally recurrent or metastatic breast cancer].

UNLABELLED: A randomized, double-blind, placebo-controlled, phase 3 trial comparing SMS 201-995 pa LAR plus tamoxifen versus tamoxifen plus placebo in women with locally recurrent or metastatic breast cancer. PATIENTS AND METHODS: Numerous studies have proved the efficacy of tamoxifen treatment in women with receptor-positive breast cancer. Preclinical and phase I/II-studies showed that tumor control can be improved if Octreotid is added. In this randomized controlled double blind phase III study women received 20 mg tamoxifen daily and either 160 mg Octreoid-Depot i. m. injection once a month or a placebo injection. Until 1998 a total of 263 women were randomized. RESULTS: The study medication was tolerated well by all patients in the treatment group (n = 133). The most frequent moderate side effects were diarrhea (n = 73), nausea (n = 26), abdominal pain (n = 19), bone pain (n = 24) and fatigue (n = 20). No patient dropped out because of these side effects. Surprisingly, several complete remissions occured. Neither the total survival nor the progression free survival was significantly different between groups. Therefore the study was stopped before the originally planned number of patients (n = 416) had been enrolled. CONCLUSION: Octreotid plus tamoxifen does not improve tumor control. It is necessary to define subgroups that might benefit from Octreotid.

Administration, Oral↗

PubMed2026

Adjuvant oxaliplatin with S-1 (SOX) versus S-1 for stage II-III gastric cancer (CAPITAL): A randomized, open-label, phase 3 trial.

BACKGROUND: Adjuvant chemotherapy following D2 gastrectomy constitutes the standard-of-care for resectable gastric or gastroesophageal junction (GEJ) carcinoma. The CAPITAL trial is a multicenter, randomized, phase 3 study, aiming to assess the efficacy and safety of adjuvant oxaliplatin plus S-1 (SOX) versus S-1 alone. METHODS: Patients with histologically confirmed pathological stage II-III gastric or GEJ adenocarcinoma after gastrectomy with D2 lymphadenectomy were randomly assigned (1:1) to receive either the SOX regimen (n = 362) or the S-1 regimen (n = 362). The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01795027). FINDINGS: The median follow-up was 74.0 months (interquartile range [IQR], 35.5-89.3). The 5-year overall survival rates were 70.9% (95% confidence interval [CI], 66.0-76.1) in the SOX group and 62.9% (95% CI, 57.8-68.5) in the S-1 group (hazard ratio [HR], 0.74; 95% CI, 0.58-0.95; p = 0.018). The 3- and 5-year disease-free survival rates were 71.2% (95% CI, 66.5-76.3) and 66.2% (95% CI, 61.2-71.6) in the SOX group, as compared with 65.1% (95% CI, 60.2-70.5) and 55.6% (95% CI, 50.4-61.3) in the S-1 group (HR, 0.76; 95% CI, 0.61-0.96). Treatment-related adverse events of grade 3-4 occurred in 87 (25%) of 349 patients in the SOX group and 45 (13%) of 347 patients in the S-1 group. The most common grade 3-4 adverse event was neutropenia, occurring in 44 (13%) of 349 patients in the SOX group and 23 (7%) of 347 patients in the S-1 group. CONCLUSIONS: The addition of adjuvant oxaliplatin to S-1 chemotherapy significantly improved overall survival and disease-free survival in patients with gastric cancer. FUNDING: This research was supported by the National Natural Science Foundation of China (82573092 and 82573387).

Humans↗

PubMed2002

Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720.

The Cancer and Leukemia Group B conducted a phase 3 trial of the P-glycoprotein modulator PSC-833 in untreated acute myeloid leukemia patients aged 60 years and older. Patients were randomized to 1 of 2 regimens, with doses determined in a prior phase 1 study, consisting of cytarabine 100 mg/m(2)/d by 7-day infusion, with daunorubicin 60 mg/m(2) and etoposide 100 mg/m(2) daily for 3 days (ADE), or daunorubicin 40 mg/m(2) and etoposide 60 mg/m(2) for 3 days with PSC-833, 2.8 mg/kg over 2 hours, and then 10 mg/kg/d by 3-day infusion (ADEP). The ADEP arm was closed after randomization of 120 patients (61 to ADE and 59 to ADEP) because of excessive early mortality. Rates of complete remission, nonresponse, and death were 46%, 34%, and 20% for ADE, versus 39%, 17%, and 44% for ADEP (P =.008). Nevertheless, disease-free survival (median 7 vs 8 months; P =.38) and overall survival (approximately 33% alive at 1 year) did not differ and were similar to historical results. Although the number of patients was limited, ADE patients whose pretreatment cells exhibited PSC-833-modulated dye efflux in vitro (n = 22) had worse outcomes than those without efflux (n = 11) (complete remission, nonresponse, and death rates of 41%, 41%, and 18%, compared with 91%, 9%, and 0%; P =.03), but with ADEP outcomes were nearly identical. Moreover, for patients with PSC-833-modulated efflux, median disease-free survival was 5 months with ADE and 14 months with ADEP (P =.07). Further modulation trials in older patients must await the design of less-toxic regimens.

Aged↗

PubMed2004

[Diagnosis of initial changes in patients suffering from rheumatoid arthritis. Two years follow up control with a low-field magnetic resonance scanner, 3-phase bone scintigraphy and conventional x-ray].

UNLABELLED: Besides conventional x-ray, in the diagnostic work up of initial changes in patients suffering from rheumatoid arthritis (RA), 3-phase bone scintigraphy (3P-Sz) is as well established as magnetic resonance imaging (MRI). The AIM of this study was to compare the diagnostic value of a newly developed low field MRI with proven methods such as conventional x-ray and 3P-Sz. PATIENTS, METHODS: 42 patients were studied using a one days protocol with 3P-Sz, MRI, and x-ray of the hands with yearly follow up examinations. Images were visually assessed by two blinded nuclear medicine physicians and radiologists and classified as RA-typical and non-RA-typical changes. All methods were compared to the summarised findings interpreted by a rheumatologist in consideration of the Ritchie articular index as gold-standard. RESULTS: 24/42 patients presented with clinical symptoms of initial changes by rheumatoid arthritis. Conventional x-ray revealed in 20/24 patients within the correct diagnosis in the study period. On the other hand 3P-Sz and low field MRI concordantly showed all 24 patients with initial changes due to RA. Time of detection showed variations with a tendency to later findings by conventional x-ray. CONCLUSIONS: In the diagnostic work up of initial changes conventional x-ray should be the first choice in imaging. Our findings suggest that MRI represents an equally sensitive method for the diagnosis of initial changes due to RA in the region of the hands as compared to the 3P-Sz. The limitation of the low field MRI is the small field of view, so we prefer 3P-Sz or high field MRI in the diagnosis of patients with suspected RA.

Arthritis, Rheumatoid↗

PubMed2002

[Diagnosis of initial changes in the hand of patients with rheumatoid arthritis--comparison between low-field magnetic resonance imaging, 3-phase bone scintigraphy and conventional x-ray].

UNLABELLED: Besides conventional X-rays, in the diagnostic work up of initial changes in patients suffering from rheumatoid arthritis (RA), 3-phase bone scintigraphy (3P-Sz) is as well established as magnetic resonance imaging (MRI). The aim of this study was to compare the diagnostic value of the newly developed low field MRI with the proven methods X-rays and 3P-Sz. METHODS: 65 patients (47f, 18m; 20-86 yrs) were studied on a one day protocol with 3P-Sz (550 MBq Tc-99m DPD), MRI and X-rays of the hands. Images were visually analysed by two blinded nuclear medicine physicians and radiologists and classified as a) RA-typical, b) inflammatory, non-RA-typical and c) non inflammatory changes. All methods were compared to 3P-Sz as golden standard. RESULTS: In comparison to 3P-Sz, low field MRI presents with almost equal sensitivity and specificity in rheumatoid-typical and inflammatory changes. Conventional X-rays revealed in arthritis-typical changes as well as in inflammatory changes a significantly lower sensitivity and also a lower negative predictive value while specificity equals the one of MRI. Quantitative analysis of 3P-Sz using ROI-technique unveiled significantly higher values in patients with rheumatoid arthritis than in those with no inflammatory changes. CONCLUSION: MRI represents an equally sensitive method in the initial diagnosis of rheumatoid-typical and inflammatory changes in the region of the hands as compared to the 3P-Sz. Besides the basic diagnosis with conventional X-rays, 3P-Sz is still the recommended method of choice to evaluate the whole body when RA is suspected. Additionally, quantitative analysis of the 3P-Sz using the ROI technique in the region of the hands reveals statistically significant results and should therefore be taken into account in the assessment of inflammatory changes.

Adult↗

PubMed1999

A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404.

PURPOSE: This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy. METHODS AND MATERIALS: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment. RESULTS: As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in the two arms seem to be due to early deaths in the BUdR arm, not related to toxicity of the treatment. CONCLUSIONS: Despite encouraging Phase 2 results with BUdR, it is unlikely that a survival benefit will be seen. A final study analysis will not be done for at least 3 more years.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2026

Adjuvant alectinib versus chemotherapy in resected ALK-positive non-small-cell lung cancer (ALINA): health-related quality-of-life and safety outcomes from a randomised, open-label, phase 3 trial.

BACKGROUND: For patients with resected, ALK-positive non-small-cell lung cancer (NSCLC), adjuvant alectinib significantly improved disease-free survival versus platinum-based chemotherapy in the global, phase 3, open-label, randomised ALINA trial. We report safety and health-related quality-of-life (HRQoL) outcomes from the ALINA trial. METHODS: Eligible patients aged 18 years or older with resected, ALK-positive, stage IB (≥4 cm)-IIIA NSCLC (per the American Joint Committee on Cancer and the Union for International Cancer Control Cancer Staging Manual 7th edition) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (1:1) via a block-stratified randomisation method to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy for four 3-week cycles. Randomisation was stratified according to disease stage and race. The primary endpoint, previously reported, was disease-free survival. Safety was a secondary endpoint and HRQoL was an exploratory endpoint. Safety was assessed by the investigator as per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5·0 until 28 days after the last alectinib dose or chemotherapy cycle. HRQoL was assessed via the Short-Form 36-item health survey version 2 (SF-36v2) questionnaire at baseline, every 3 weeks to week 12, then every 12 weeks until disease recurrence, consent withdrawal, death, or week 96. Norm-based scoring was applied; clinically meaningful changes were defined using the SF-36v2 manual. Safety was assessed in the safety-evaluable population and HRQoL in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT03456076) and is ongoing. FINDINGS: Between Aug 16, 2018, and Dec 8, 2021, 257 patients were assigned to receive alectinib (n=130) or chemotherapy (n=127). 123 (48%) patients were male and 134 (52%) were female; 143 (56%) were Asian. The safety-evaluable population comprised 128 patients who received alectinib and 120 patients who received chemotherapy; median duration of safety follow-up was 24·8 months (IQR 22·0-24·9) in the alectinib group and 3·7 months (IQR 3·7-3·8) in the chemotherapy group. The safety of adjuvant alectinib was generally consistent with its known profile. The most common grade 3-4 adverse events were blood creatine phosphokinase increased (eight [6%] of 128), alanine aminotransferase increased (two [2%] of 128), and blood bilirubin increased (two [2%] of 128) in the alectinib group, and neutrophil count decreased (12 [10%] of 120), neutropenia (ten [8%] of 120), and nausea (five [4%] of 120) in the chemotherapy group. Serious treatment-related adverse events occurred in two (2%; one each with appendicitis and pneumonitis) of 128 patients in the alectinib group and eight (7%) of 120 patients in the chemotherapy group ( most common were gastrointestinal disorders in three [3%] patients). No deaths due to adverse events were reported in either group. There were fewer discontinuations due to adverse events with alectinib (seven [5%]) versus chemotherapy (15 [13%]). A clinically meaningful difference in improvement from baseline was seen at week 12 for bodily pain, role physical, mental health, social functioning, and vitality SF-36v2 domains with alectinib; improvements in physical and mental HRQoL were maintained over 2 years of active treatment (at week 96, mean Mental Component Summary score: 49·9 [SD 10·4]; mean Physical Component Summary score: 48·8 [SD 7·2]) and reached levels similar to the general population (population norm: 50). INTERPRETATION: For patients with resected ALK-positive NSCLC, adjuvant alectinib had a manageable safety profile; HRQoL improved and was maintained over 2 years of active treatment. Together with the disease-free survival benefit seen in ALINA, these data support adjuvant alectinib as an important new standard-of-care for patients with resected ALK-positive NSCLC. FUNDING: F Hoffmann-La Roche.

Adult↗

PubMed1989

Combined therapy for resectable head and neck cancer. A phase 3 intergroup study.

This Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeastern Cancer Study Group) phase 3 randomized prospective trial was opened for registration January 1985. It is an evaluation of the role of chemotherapy for previously untreated advanced stage resectable squamous cell carcinoma of the head and neck. As of March 1, 1988, there has been a total of 535 patients registered. There are 266 patients analyzable with 133 in each treatment group. The surgical, chemotherapy, and radiation therapy toxic reactions are in the tolerable range with the worst toxic reactions reported in those patients receiving both surgery and radiation therapy. Compliance continues to be a major challenge to patient accrual. The most common cause for cases not being randomized involves positive margins of surgical resection. Patient refusal or surgical complications are other common reasons.

Antineoplastic Agents↗

PubMed2007

[Imaging in the early diagnosis of changes in the hand of patients suffering from rheumatoid arthritis. Is ultrasound a true alternative for low-field magnetic resonance scanning, 3-phase bone scintigraphy and conventional x-rays?].

PURPOSE: Besides the use of conventional x-rays in the diagnostic work-up of initial changes in patients suffering from rheumatoid arthritis (RA), 3-phase bone scintigraphy (3P-Sz) is as well established as magnetic resonance imaging (MRI). The aim of this study was to compare the diagnostic value of ultrasound of the hands with proven methods such as conventional x-rays, low-field MRI and 3P-Sz. METHODS: A total of 30 patients were studied using a 1 day protocol with ultrasound, 3P-Sz, MRI and x-ray of the hands. Images were visually assessed by two blinded nuclear medicine physicians and radiologists and classified as RA typical and non-RA typical changes. All methods were compared to the summarized findings interpreted by a rheumatologist after 2 years. RESULTS: Of the 30 patients, 19 presented with clinical symptoms of initial changes due to rheumatoid arthritis. Ultrasound revealed 14/19 patients with the correct diagnosis. Conventional x-rays indicated 11/19 patients, while 3P-Sz (100%) and low-field MRI (95%) showed high sensitivity. It was possible to differentiate between inflammation and inconspicuous findings. CONCLUSIONS: An experienced examiner can use ultrasound effectively for the initial diagnosis of RA. Based on its low cost, ultrasound is a valid alternative to conventional x-rays.

Adult↗

PubMed2006

Longitudinal population analysis of dual infection with recombination in two strains of HIV type 1 subtype B in an individual from a Phase 3 HIV vaccine efficacy trial.

This study documents a case of coinfection (simultaneous infection of an individual with two or more strains) of two HIV-1 subtype B strains in an individual from a Phase 3 HIV-1 vaccine efficacy trial, conducted in North American and the Netherlands. We examined 86 full-length gp120 (env) gene sequences from this individual collected from nine different time points over a 20-month period. We estimated evolutionary relationships using maximum likelihood and Bayesian methods and inferred recombination breakpoints and recombinant sequences using phylogenetic and substitutional methods. These analyses identified two strongly supported monophyletic clades (clades A and B) of 14 and 69 sequences each and a small paraphyletic recombinant clade of three sequences. We then studied the genetic characteristics of these lineages by comparing estimates of genetic diversity generated by mutation and recombination and adaptive selection within a coalescent and maximum likelihood framework. Our results suggest significant differences on the evolutionary dynamics of these strains. We then discuss the implications of these results for vaccine development.

AIDS Vaccines↗

PubMed2026

RENOIR phase 3 rituximab-lenalidomide vs rituximab as maintenance treatment in relapsed/refractory follicular lymphoma.

Maintenance treatment in older patients with relapsed or refractory (R/R) follicular lymphoma (FL) remains an area of investigation. RENOIR was a multicenter, phase 3, open-label randomized trial conducted by the Fondazione Italiana Linfomi (FIL) in older patients with R/R FL after 1 or 2 previous therapies. Patients achieving partial response or complete response (CR) after 4 to 6 cycles of standard rituximab (R)-based chemotherapy were randomized 1:1 to maintenance with R alone (standard arm) or R plus lenalidomide (R2; experimental arm). The primary end point was 2-year progression-free survival (PFS) from randomization, with an expected hazard ratio (HR) of 0.5. A total of 152 patients (median age, 71 years) were enrolled. After induction, 129 (85%) achieved an overall response (CR, 58%) and were randomized to R (n = 65) or R2 (n = 64). At a median follow-up of 68 months, the 2-year PFS was 73% in the R2 arm and 64% in the R arm. An unplanned hypothesis-generating subgroup analysis showed a greater 2-year PFS benefit with R2 in patients aged <70 years: R2, 96% vs R, 69%. Two-year overall survival rates were similar (R2, 80% vs R, 89%). Grade 3/4 adverse events were more frequent in R2, mainly neutropenia and gastrointestinal disorders. In conclusion, the primary end point of the study was not met, and R2 maintenance did not significantly improve 2-year PFS in older patients with R/R FL, although a numerical benefit was observed. R2 showed a more favorable benefit-risk profile in patients aged <70 years, whereas in older patients careful consideration of individual tolerability is warranted. This trial was registered at www.clinicaltrials.gov as NCT02390869.

Humans↗

PubMed2002

Willingness to participate and enroll in a phase 3 preventive HIV-1 vaccine trial.

OBJECTIVES: To assess the extent to which HIV-negative cohort study participants would be willing to participate (WTP) in future HIV vaccine trials, to explore enrollment into an ongoing phase 3 HIV vaccine trial, and to assess changing WTP in such trials over time. METHODS: The Vanguard Project is a prospective study of gay and bisexual men in the greater Vancouver region, British Columbia, Canada. Sociodemographic characteristics, sexual risk behavior, beliefs around HIV, and reasons for not participating in the AIDSVAX B/B trial were collected from self-administered questionnaires. Contingency table analysis compared subjects who were WTP with subjects who were not WTP. Logistic regression analyses identified possible predictors of WTP. A subset analysis was conducted to assess changes in WTP in 2001 versus 1997. RESULTS: Of 440 respondents, 214 (48.6%) were WTP, and 97 (22.0%) were not WTP. Those WTP were disadvantaged, sexually risky, and had a high-perceived HIV risk (all p <.05). Reasons for not participating in the AIDSVAX B/B trial included fear of health problems and having missed the deadline for enrollment (all p < 0.05). Multivariate analysis revealed that having had a regular sex partner (adjusted odds ratio, 0.48 [confidence interval, 0.25-0.92]) was a negative predictor whereas having a high-perceived HIV risk (adjusted odds ratio, 5.35 [confidence interval, 1.57-18.25]) was a positive predictor of WTP. Comparing WTP in 2001 with that in 1997, 24% of 100 participants who had been previously WTP were now not WTP. CONCLUSION: Improving community and participant knowledge about preventive HIV vaccine trials may help ensure informed consent. However, whether informing potential participants will reverse or contribute to the declining trend in WTP observed in this cohort warrants further investigation.

AIDS Vaccines↗