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Results for “phase 3”

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PubMed2026

Cabozantinib for advanced grade 3 neuroendocrine tumors: subgroup analysis of the phase 3 CABINET trial (Alliance A021602).

Well-differentiated grade 3 neuroendocrine tumors (NETs) have recently been described as a distinct category, and randomized data regarding efficacy of therapy for these patients are scarce. In the phase 3 CABINET trial, cabozantinib improved PFS compared with placebo in patients with advanced, previously treated, progressive extra-pancreatic NETs (epNETs) and pancreatic NETs (pNETs) of all grades. Here, we evaluate if these results remain consistent in a subgroup of patients with well-differentiated G3 NETs. Patients with locally advanced or metastatic epNETs or pNETs were randomized 2:1 in independent cohorts to receive cabozantinib 60 mg daily vs placebo. We analyzed outcomes of the subset of patients with G3 NETs (Ki-67 > 20%), combining patients in the pNET and epNET cohorts due to small sample sizes. Twenty-four patients had G3 NETs, 16 randomized to cabozantinib and 8 to placebo. Primary sites included pancreas (n = 12), GI tract (n = 7), unknown primary sites (n = 3), and lung/thymus (n = 2). Median PFS for patients with G3 NETs treated with cabozantinib was 7.9 vs 3 months with placebo (HR = 0.15, 95% CI: 0.04-0.57, 1-sided log-rank P = 0.0034). The confirmed overall radiographic response rate was 25% (4/16) with cabozantinib vs 0% (0/8) with placebo. Safety outcomes were consistent with published data for the trial as a whole. Subset analysis of the CABINET trial showed improved PFS associated with cabozantinib vs placebo for G3 NETs of pancreatic and extra-pancreatic origin. Despite limited numbers, these results suggest that cabozantinib can be an effective option for patients with advanced G3 NETs. ClinicalTrials.gov Identifier: NCT03375320.

Humans↗

PubMed2003

An investigation on a broad infrared band with the maximum at approximately 1300 cm(-1) in magnesia cement, phase 3.

In magnesia cement, phase 3, a broad and strong infrared band was observed with the maximum at approximately 1300 and 1050 cm(-1) in the H and D systems, respectively. To clarify the origin of the 1300 cm(-1) band the temperature dependency of the infrared spectra of the H system was observed and the spectra analyzed on the basis of a strong vibrational coupling of the OH stretching with lattice modes. The fitting was quite well, giving rise to the origin of the 1300 cm(-1) band of the OH stretching.

Magnesium Oxide↗

PubMed1999

Clinical application of an integrated 3-phase mapping technique for localization of the site of origin of idiopathic ventricular tachycardia.

BACKGROUND: Radiofrequency (RF) catheter ablation provides curative treatment for idiopathic ventricular tachycardia (VT). METHODS AND RESULTS: Nineteen consecutive patients with an idiopathic VT underwent RF catheter ablation. An integrated 3-phase mapping approach was used, consisting of the successive application of online 62-lead body surface QRS integral mapping, directed regional paced body surface QRS integral mapping, and local activation sequence mapping. Mapping phase 1 was localization of the segment of VT origin by comparing the VT QRS integral map with a database of mean paced QRS integral maps. Mapping phase 2 was body surface pace mapping during sinus rhythm in the segment localized in phase 1 until the site at which the paced QRS integral map matched the VT QRS integral map was identified (ie, VT exit site). Mapping phase 3 was local activation sequence mapping at the circumscribed area identified in phase 2 to identify the site with the earliest local endocardial activation (ie, site of VT origin). This site became the ablation target. Ten VTs were ablated in the right ventricular outflow tract, 2 at the basal LV septum, and 7 at the midapical posterior left ventricle. A high long-term ablation success (mean follow-up duration, 14+/-9 months) was achieved in 17 of the 19 patients (89%) with a low number of RF pulses (mean, 3.3+/-2.2 pulses per patient). CONCLUSIONS: This prospective study shows that integrated 3-phase mapping for localization of the site of origin of idiopathic VT offers efficient and accurate localization of the target site for RF catheter ablation.

Adult↗

PubMed2006

Assessment of the therapeutic response of hepatocellular carcinoma treated with transcatheter arterial chemoembolization: comparison of contrast-enhanced sonography and 3-phase computed tomography.

OBJECTIVE: The purpose of this study was to compare contrast-enhanced sonography with 3-phase computed tomography (CT) in assessing the therapeutic response of hepatocellular carcinomas (HCCs) treated with transcatheter arterial chemoembolization (TACE). METHODS: Twenty-nine nodular HCCs treated with TACE were examined with contrast-enhanced sonography, 3-phase helical CT, and conventional angiography. Contrast-enhanced sonographic and CT findings were interpreted separately and prospectively for the presence or absence of contrast enhancement in the treated HCCs. Conventional angiography served as the reference standard. RESULTS: Intratumoral enhancement was seen in 19 HCCs (61%) on contrast-enhanced sonography and 12 HCCs (39%) on CT. Enhancement patterns on sonography were blush in 8 (42%), branching in 2 (11%), nodular in 4 (21%), and stippled in 5 (26%). Of the 19 HCCs with intratumoral enhancement on contrast-enhanced sonography, 13 (68%) showed tumor staining on angiography. Of the 12 HCCs without intratumoral enhancement on sonography, 1 (8%) showed tumor staining on angiography. The sensitivity and specificity of contrast-enhanced sonography in depicting flow in HCCs treated with TACE were 93% and 65%, respectively. The sensitivity and specificity of 3-phase CT were 64% and 100%. CONCLUSIONS: Contrast-enhanced sonography is a more sensitive imaging method than 3-phase CT in depicting vascularity in HCCs treated with TACE.

Adult↗

PubMed2004

Clinical relevance of adjunctive minocycline microspheres in patients with chronic periodontitis: secondary analysis of a phase 3 trial.

BACKGROUND: A recent Phase 3 trial demonstrated that adjunctive treatment with minocycline microspheres resulted in significant reductions in patient mean probing depths as compared to scaling and root planing (SRP) alone. The objective of the present study was to evaluate clinical relevance of these changes within the trial using proposed site-based criteria. METHODS: A total of 499 patients with moderate to advanced chronic periodontitis were enrolled in a multi-center trial and randomized to either: 1) SRP alone or 2) SRP plus minocycline microspheres. Subjects received complete probing examinations including the measurement of probing depths at baseline, and 1 and 3 months. Probing depth reductions were tabulated by treatment, examination time, and baseline depths, and inter-group differences were evaluated with logistic regression models for correlated data. RESULTS: Significantly more sites treated with adjunctive minocycline microspheres exhibited probing depths < 5 mm at 1 (P = 0.0009) and 3 (P = 0.01) months as compared to sites treated with SRP alone, both in the overall population and in smokers. In addition, significantly more sites decreased by 1, 2, or 3 mm in the adjunctive minocycline group than in the SRP alone group at 1 and 3 months, both overall as well as in smokers (P < 0.05). CONCLUSION: This secondary analysis indicates that treatment with SRP plus minocycline microspheres is consistently more effective than SRP alone in providing clinically relevant site-based responses in patients with chronic periodontitis.

Anti-Bacterial Agents↗

PubMed2003

Predicting the outcome of distraction osteogenesis by 3-phase bone scintigraphy.

UNLABELLED: Distraction osteogenesis is an effective method for lengthening long bones and filling bone defects that result from bone resection. Insufficiency of bone consolidation in the distraction segment is problematic. In this study, we examined whether 3-phase bone scintigraphy can predict the outcome of distraction osteogenesis. We also investigated the effects of chemotherapy and surgical treatment on distraction osteogenesis. METHODS: We performed 3-phase bone scintigraphy on 60 patients (9 high-grade malignant bone tumors as group A, 11 low-grade malignant or benign tumors as group B, 40 nontumoral conditions as group C) with distraction osteogenesis at the lengthening phase of the long bones. By setting the region of interest on the distraction segment and contralateral normal area, we calculated the perfusion index (PI), the uptake ratio of the blood-pool image (BPR), and the uptake ratio of the delayed image (DR). Patients were classified into poor and good consolidation groups from the radiographic findings of the distraction segment. RESULTS: Good to fair correlations were obtained between the PI and BPR, the PI and DR, and the BPR and DR (r = 0.65, 0.45, and 0.57, respectively). The PI and BPR indicated no significant differences among group A-C (1.7 +/- 0.6, 2.1 +/- 0.7, and 1.8 +/- 0.8 in PI, respectively; 1.8 +/- 1.1, 1.9 +/- 0.5, and 2.0 +/- 0.7, in BPR, respectively). The DR of group A (2.4 +/- 1.2) was significantly lower than that of group B (6.3 +/- 1.8; P = 0.001) and group C (5.9 +/- 2.8; P < 0.001). Eleven patients were classified in the poor consolidation group. The other 49 patients showed good consolidation. The poor consolidation group showed lower values in all indices obtained by 3-phase bone scintigraphy than the good consolidation group. The optimal cutoff levels, sensitivity, specificity, and accuracy of each index for detection of patients with poor consolidation were as follows: 1.1, 36%, 90%, and 80% in the PI, respectively; 1.2, 55%, 94%, and 87% in the BPR, respectively; and 2.2, 82%, 96%, and 93% in the DR, respectively. CONCLUSION: Three-phase bone scintigraphy is a promising method for the assessment of distraction osteogenesis. The delayed image of 3-phase bone scintigraphy, especially, is an excellent modality for predicting the outcome of distraction osteogenesis.

Adolescent↗

PubMed2026

Microbiological analysis and whole-genome sequencing of Neisseria gonorrhoeae from the microbiological failures in the international, zoliflodacin, phase 3, clinical trial for treatment of uncomplicated urogenital gonorrhoea: a retrospective, genomic, observational study.

BACKGROUND: Zoliflodacin, a first-in-class oral bacterial, DNA gyrase (GyrB) inhibitor, showed non-inferiority to ceftriaxone combined with azithromycin in a recent large international, phase 3, randomised controlled trial for treatment of uncomplicated urogenital gonorrhoea. The aim of this study was to describe the microbiological and whole-genome sequencing (WGS) analyses of paired baseline (pre-treatment) and test-of-cure (TOC) gonococcal isolates from the zoliflodacin phase 3, randomised controlled trial to further characterise and evaluate the protocol-specified microbiological failures with zoliflodacin (n=22) or ceftriaxone and azithromycin (n=1). METHODS: In this retrospective, genomic, observational study, results from antimicrobial susceptibility testing (agar dilution method) of isolates (n=960; 936 baseline isolates from 763 participants and 24 TOC isolates [23 with a paired baseline isolate in the same anatomical site] from 20 participants) collected during the zoliflodacin phase 3, randomised controlled trial done in 16 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA (Nov 6, 2019-March 16, 2023) are described. WGS analysis was performed on paired baseline and TOC isolates from participants with microbiological failures (zoliflodacin 44 isolates [19 participants]; ceftriaxone and azithromycin two isolates [one participant]), and the three baseline isolates with highest zoliflodacin minimum inhibitory concentration (MIC 0·5 mg/L). FINDINGS: All isolates were inhibited by the same zoliflodacin concentrations (MICs ≤0·008 to 0·5 mg/L) as wild-type strains cultured internationally in 2013-23. In participants with a microbiological failure after zoliflodacin treatment (n=22, 19 participants), zoliflodacin MIC values for baseline and TOC isolates were similar, and resistance selection was lacking. WGS showed that five (23%) of 22 infections (95% CI 10-43 [in four participants]) of zoliflodacin microbiological failures had different strains at TOC versus baseline. In 17 zoliflodacin microbiological failures (15 participants), isolates at baseline and TOC were indistinguishable. 13 of these 17 microbiological failures, corresponding to 59% (95% CI 39-77; 13 of 22) of all zoliflodacin microbiological failures, were in urogenital or rectal sites in 11 participants and the isolates had zoliflodacin MICs less than or equal to 0·008 to 0·25 mg/L. The single microbiological failure after ceftriaxone and azithromycin treatment had different strains at TOC versus at baseline. No sequenced isolates had mutations associated with elevated zoliflodacin MICs. INTERPRETATION: In the zoliflodacin phase 3, randomised controlled trial, 23% of the zoliflodacin microbiological failures and the single ceftriaxone and azithromycin microbiological failure had different gonococcal strains at TOC versus baseline, which suggests reinfections and not treatment failures. In addition, 59% of the zoliflodacin microbiological failures, all in anogenital sites, had no obvious microbiological explanation based on the low zoliflodacin MICs, previous pharmacodynamic studies, and no evidence of resistance selection after zoliflodacin therapy. A reinfection as the cause for these microbiological failures could not be excluded. We recommend that WGS is implemented in future randomised controlled trials for gonorrhoea treatment to further evaluate possible microbiological failures, exclude reinfections (to avoid underestimating the cure rates), and characterise antimicrobial resistance determinants. FUNDING: GARDP through grants from Germany BMFTR (03KA1831), UK DHSC as part of GAMRIF, Japan MHLW, the Netherlands' Ministry of Health, Welfare and Sport and Directorate-General for International Cooperation, the Federal Office of Public Health of Switzerland, the Canton of Geneva, Switzerland, and Örebro University Hospital, Sweden.

Humans↗

PubMed2006

Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial.

The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.

Acute Disease↗

PubMed2005

Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of 5% imiquimod cream compared with vehicle in the treatment of actinic keratosis (AK). DESIGN: Two phase 3 randomized, double-blind, parallel-group, vehicle-controlled studies. SETTING: Twenty-six ambulatory care offices, including dermatologists in private practice or research centers. PATIENTS: Four hundred ninety-two patients, 18 years and older, with 4 to 8 AK lesions in a 25-cm(2) treatment area on the face or the balding scalp were randomized; an additional 162 patients underwent screening but were ineligible. INTERVENTIONS: Patients applied 5% imiquimod (Aldara) or vehicle cream to the treatment area once daily, 3 times per week, for 16 weeks, followed by an 8-week posttreatment period. MAIN OUTCOME MEASUREMENTS: Complete clearance rate (proportion of patients at the 8-week posttreatment visit with no clinically visible AK lesions in the treatment area), partial clearance rate (proportion of patients at the 8-week posttreatment visit with a >/=75% reduction in the number of baseline AK lesions in the treatment area), and frequency and severity of adverse events and local skin reactions were measured. RESULTS: Complete and partial clearance rates for imiquimod-treated patients (48.3% and 64.0%, respectively) were clinically and statistically significantly higher than for vehicle-treated patients (7.2% and 13.6%, respectively). The median percentage reduction of baseline lesions was 86.6% for the imiquimod-treated group and 14.3% for the vehicle-treated group. CONCLUSION: The 5% imiquimod cream dosed 3 times weekly for 16 weeks is safe and effective for the treatment of AK.

Administration, Topical↗

PubMed2006

Late-phase 3 EAD. A unique mechanism contributing to initiation of atrial fibrillation.

Early (EAD) and delayed (DAD) afterdepolarizations-induced triggered activity is capable of initiating and maintaining cardiac arrhythmias. EAD-induced triggered responses are traditionally thought to be involved in the generation of ventricular arrhythmias under long QT conditions and are precipitated by bradycardia or long pauses. In contrast, DAD-induced triggered activity commonly underlies arrhythmias precipitated by tachycardia. Spontaneous release of calcium from the sarcoplasmic reticulum (SR) secondary to cellular calcium overload induces DADs and some forms of EADs. Recent studies from our laboratory have uncovered a novel mechanism giving rise to triggered activity, termed "late-phase 3 EAD," which combines properties of both EAD and DAD, but has its own unique character. Late-phase 3 EAD-induced triggered extrasystoles represent a new concept of arrhythmogenesis in which abbreviated repolarization permits "normal SR calcium release" to induce an EAD-mediated closely coupled triggered response, particularly under conditions permitting intracellular calcium loading. This review briefly describes the mechanisms and properties of late-phase 3 EADs, how they differ from conventional EADs and DADs, as well as their role in the initiation of cardiac arrhythmias, such as atrial fibrillation.

Action Potentials↗

PubMedDate not supplied

Safety outcomes in meta-analyses of phase 2 vs phase 3 randomized trials: Intracranial hemorrhage in trials of bolus thrombolytic therapy.

CONTEXT: Recent studies have reported disagreement between meta-analysis of small trials and subsequent large trials addressing the same question. However, disagreement for uncommon but serious adverse safety outcomes has not been examined. OBJECTIVE: To explore disagreement for serious adverse safety (intracranial hemorrhage [ICH]) and efficacy outcomes between meta-analysis of phase 2 (small) vs meta-analysis of phase 3 (large) randomized controlled trials comparing the efficacy of bolus thrombolytic therapy with infusion for acute myocardial infarction (AMI). DATA SOURCES: Electronic databases (MEDLINE, Cochrane Database of Clinical Trials) between January 1980 and December 1999 using the search terms thrombolysis, thrombolytic therapy, and myocardial infarction; conference proceedings; and reference lists. STUDY SELECTION: Fifteen randomized trials comparing thrombolytic agents administered by bolus injection with standard infusion therapy in patients with AMI. DATA EXTRACTION: Data on ICH, other causes of stroke, total mortality, and reinfarction were independently extracted from each study by 2 observers. DATA SYNTHESIS: Meta-analysis of 9 phase 2 trials (n = 3956) revealed a lower risk of ICH with bolus thrombolytic therapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.27-1.01), which was not statistically significant. Meta-analysis of 6 phase 3 trials (n = 62 673) indicated a significant increase in risk of ICH (OR, 1.25; 95% CI, 1.06-1.49). These results were significantly different (P =.01). There was no disagreement for efficacy outcomes. Phase 2 trials included younger and heavier patients with lower baseline blood pressures, and were more often open-label. Subgroup analyses suggested that each of these factors was associated with a lower estimate of risk of ICH with bolus agents. CONCLUSIONS: Our results suggest that when therapeutic interventions are associated with a potential for uncommon but serious adverse safety outcomes, there may be differences between small phase 2 and large phase 3 trials that result in their disagreement for safety but not necessarily efficacy outcomes. Further investigation of the frequency and causes of disagreement between small and large trials for safety outcomes is warranted.

Clinical Trials, Phase II as Topic↗

PubMed2003

Design and methodology of the phase 3 trials for the clinical development of strontium ranelate in the treatment of women with postmenopausal osteoporosis.

The phase 3 program for strontium ranelate, a new oral agent in the treatment of women with postmenopausal osteoporosis, was aimed to assess the efficacy and safety of the daily oral dose of 2 g. This program was conducted in 12 countries, involved 75 centers, and was structured in 3 studies: FIRST (Fracture International Run-in for Strontium ranelate Trial), SOTI (Spinal Osteoporosis Therapeutic Intervention study) and TROPOS (TReatment Of Peripheral OSteoporosis). FIRST, a run-in open study, was designed to start the normalization of the calcium and vitamin D status of the patients, check all entry criteria, and ensure inclusion of a sufficient number of well-motivated patients in either one of the two therapeutic intervention protocols, SOTI or TROPOS: FIRST included 9,196 patients. SOTI and TROPOS were prospective, randomized, double-blind clinical trials comparing, in two parallel groups, the daily oral dose of 2 g of strontium ranelate with placebo, the patients of both groups receiving calcium and vitamin D according to their own deficiencies. The main objective of SOTI and TROPOS was to demonstrate a reduction in the incidence of postmenopausal women experiencing a new osteoporotic fracture (vertebral fracture in SOTI and nonvertebral fracture in TROPOS) over a 3-year treatment period, the total duration of the studies being 5 years. SOTI included 1,649 women with at least one osteoporotic vertebral fracture at inclusion and a lumbar BMD </=0.840 g/cm(2). TROPOS included 5,091 women with a femoral neck BMD </=0.600 g/cm(2). The phase 3 program for the clinical development of strontium ranelate in women with postmenopausal osteoporosis is a long-term program with the main statistical analysis after 3 years of treatment. Its aim is to demonstrate the effect of strontium ranelate on the axial and appendicular skeleton as well as its tolerability in osteoporotic patients with replete calcium and vitamin D stores.

Aged↗

PubMed2004

Recruitment and baseline epidemiologic profile of participants in the first phase 3 HIV vaccine efficacy trial.

OBJECTIVE: To describe recruitment and baseline epidemiologic characteristics of volunteers in the first phase 3 placebo-controlled trial of a recombinant gp120 HIV vaccine (AIDSVAX B/B). METHODS: Volunteers were gay/bisexual men or women at risk for sexually transmitted HIV infection. Recruitment strategies, demographics, and risk factors were assessed. HIV status was determined by standard HIV-1 antibody assays. Seronegative/viremic HIV infection at enrollment was determined using the HIV-1 nucleic acid test. RESULTS: From June 1998 through October 1999, 5417 of 7185 volunteers screened were enrolled at 61 sites in the United States, Canada, and The Netherlands. Successful recruitment methods included distribution of study information at gay venues, advertising and media coverage, and referrals from volunteers. Most volunteers were altruistically motivated, men (98%), young (median, 36 years), white (83%), well educated (61% college education or more), and at high risk for HIV during the 6 months before enrollment. At baseline, 14 were HIV infected (12 were seronegative but viremic; 2 were seropositive and viremic). CONCLUSION: Men and women at high risk for sexually transmitted HIV infection were successfully recruited for the first phase 3 HIV vaccine efficacy trial. Knowledge of recruitment and baseline epidemiologic characteristics of participants in this trial will provide valuable guidance for designing and conducting future trials.

AIDS Vaccines↗

PubMed2003

Reinduction of atrial fibrillation immediately after termination of the arrhythmia is mediated by late phase 3 early afterdepolarization-induced triggered activity.

BACKGROUND: Atrial fibrillation (AF) at times recurs immediately after termination of the arrhythmia. The mechanism(s) responsible for the extrasystole that reinduces AF is largely unknown. We hypothesized that abbreviation of action potential duration (APD) would permit very rapid rates of excitation, known to induce intracellular calcium loading, which in turn could promote delayed and/or early afterdepolarizations (EADs). METHODS AND RESULTS: Acetylcholine (ACh, 1 micromol/L) was used to abbreviate atrial APD and permit rapid-pacing induction of AF in isolated coronary-perfused canine right atria. Transmembrane action potentials, pseudo-ECG, and tension development were recorded. AF or rapid pacing was associated with an increase in tonic tension. Termination of AF or rapid pacing (cycle length, 150 to 80 ms) resulted in a dramatic rise of phasic tension, prolongation of repolarization of the initial beats at the regular rate (cycle length, 700 ms), and the development of late phase 3 EADs and extrasystoles. These extrasystoles initiated AF in 15 cases (involving 9 right atria) within the first 11 seconds after termination of AF or rapid pacing. This novel EAD mechanism is observed only in association with marked APD abbreviation. The calcium channel blocker nifedipine reduced, and the sarcoplasmic reticulum calcium release blocker ryanodine eliminated, the post-rapid pacing-induced increase in phasic tension, late phase 3 EADs, and extrasystoles that initiate AF. CONCLUSIONS: These data suggest that calcium overload conditions present after termination of vagally mediated AF contribute to the development of late phase 3 EAD-induced triggered activity and that this mechanism may be responsible for the extrasystolic activity that reinitiates AF.

Acetylcholine↗

PubMed1987

[Value of 3-phase skeletal scintigraphy in the diagnosis of bone metastases].

51 patients suffering from 125 bone metastases of various primary tumors were investigated with three-phase skeletal scintigraphy in an attempt to define criteria characteristic for bone metastases with regard to differential diagnosis. During the 3 phases of imaging, the metastases exhibited 5 different patterns of activity concentration. None of these patterns was correlated either to the size and morphological X-ray appearance of the metastases or to the histology of the primary tumors. The intensity of radionuclide concentration was also varying. The most frequent patterns of activity concentration were increased uptake during the blood-pool phase and skeletal phase combined with absence of concentration during the angiographical phase (43%), and increased uptake during all of the 3 phases (34%). In this series, a pattern of scintigraphical findings characteristic for bone metastases or helpful in the differential diagnosis could not be determined. In our experience, three-phase skeletal scintigraphy is not useful in the diagnosis and differential diagnosis of bone metastases.

Bone Neoplasms↗

PubMed2000

Prediction of the outcome of a phase 3 clinical trial of an antischizophrenic agent (quetiapine fumarate) by simulation with a population pharmacokinetic and pharmacodynamic model.

A completed phase 3 trial result was simulated 100 times on the basis of a simulation model of quetiapine fumarate (Seroquel), an antischizophrenic agent. The simulation was executed by analysts who were completely blinded from results of the actual trial until after the simulations were submitted to the holder of the trial results. Data from two clinical investigations of quetiapine in patients with schizophrenia were analyzed by use of nonlinear mixed effects modeling to derive a population pharmacokinetic- and pharmacodynamic-based simulation model. The time course of quetiapine concentrations was described by use of a one-compartment open linear pharmacokinetic model with first-order absorption and elimination. The combination of an inhibitory maximum effect pharmacodynamic model for the active treatment effect and a linear function of time for the placebo effect characterized the observed time course of change in the Brief Psychiatric Rating Scale. Simulation results were compared with those in the actual trial to evaluate how well the simulations predicted the outcome. The actual trial results for all doses except the placebo group fell within the predicted Brief Psychiatric Rating Scale scores +/- 1 SE. Unlike the phase 2 trial, from which the pharmacokinetic/pharmacodynamic model was developed, the placebo group in the actual phase 3 trial showed deterioration of Brief Psychiatric Rating Scale scores with time. We conclude that variable placebo responses observed in short-term studies of schizophrenia provide an inadequate basis for the modeling and simulation of placebo subjects in clinical trials. Knowledge of the range of placebo response observed in other studies may have provided an improved basis for the placebo effect model. The model for active drug produced adequate predictions of the actual trial outcomes.

Algorithms↗

PubMed2003

Horizontal transmission of rhesus monkey rotavirus-based quadrivalent vaccine during a phase 3 clinical trial in Caracas, Venezuela.

During a phase 3 clinical trial of rhesus monkey rotavirus-based quadrivalent vaccine in Venezuela, 2207 infants received 3 oral doses of vaccine (4 x 105 plaque-forming units/dose) or placebo at ages approximately 2, 3, and 4 months; 219 (14%) of 1537 stools obtained during 1550 diarrheal episodes in postvaccination surveillance were rotavirus-positive by enzyme-linked immunosorbent assay. With the use of various VP7 and VP4 primers for genotyping purposes, 213 of 219 rotavirus-positive stools were analyzed by reverse-transcription polymerase chain reaction. Twenty-nine (14%) of 213 rotavirus-positive stools contained at least 2 distinct rotavirus strains: a low-titered vaccine strain(s) and a second strain that, when possible, was studied further and found to be a wild-type rotavirus strain. The titer of vaccine viruses in 19 stools that plaqued directly in cell cultures ranged from 10(1) to 10(3) plaque-forming units/0.5 mL of a 10% stool suspension. Reassortants of vaccine virus and wild-type human rotavirus were not detected.

Animals↗

PubMed2005

Ewing sarcoma of the rib with normal blood flow and blood pool imagings on a 3-phase bone scan.

Ewing sarcoma is the second most common pediatric malignant bone tumor. It usually presents as a hot spot on a 3-phase bone scan as a result of increased vascularity of the tumor and new bone formation. However, aggressive Ewing sarcoma can also appear as a cold lesion. We present the features of a Ewing sarcoma of the rib on a 3-phase bone scan in a child who was being investigated for rib fracture after trauma.

Blood Flow Velocity↗