interim analysis
Recently Published Documents


TOTAL DOCUMENTS

2952
(FIVE YEARS 884)

H-INDEX

68
(FIVE YEARS 16)

2022 ◽  
pp. 088307382110476
Author(s):  
Eric Segal ◽  
Katherine Moretz ◽  
James Wheless ◽  
Patricia Penovich ◽  
Marcelo Lancman ◽  
...  

PROVE is a retrospective, phase IV study assessing retention, dosing, efficacy, and safety of perampanel when administered to patients during routine clinical care. We report an interim analysis of preadolescent (1 to <12 years) and adolescent (12 to <18 years) patients. Data were obtained from medical records of patients with epilepsy initiating perampanel after January 1, 2014; cut-off date for this analysis was October 10, 2018. Overall, 151 preadolescent and 183 adolescent patients were included. Retention rates following 24 months on perampanel were 42.5% (preadolescent subgroup; n = 31/73) and 55.7% (adolescent subgroup; n = 54/97). Treatment-emergent adverse events occurred in 53 (35.1%) preadolescent (most common: aggression, irritability, and somnolence) and 78 (42.6%) adolescent patients (most common: somnolence, aggression, and dizziness). These data indicate that daily oral doses of perampanel are generally well tolerated during routine clinical care, with favorable retention rates for ≤2 years, in patients aged 1 to <18 years.


PLoS Medicine ◽  
2021 ◽  
Vol 18 (12) ◽  
pp. e1003875
Author(s):  
Fred C. Semitala ◽  
Jillian L. Kadota ◽  
Allan Musinguzi ◽  
Juliet Nabunje ◽  
Fred Welishe ◽  
...  

Background Scaling up shorter regimens for tuberculosis (TB) prevention such as once weekly isoniazid–rifapentine (3HP) taken for 3 months is a key priority for achieving targets set forth in the World Health Organization’s (WHO) END TB Strategy. However, there are few data on 3HP patient acceptance and completion in the context of routine HIV care in sub-Saharan Africa. Methods and findings The 3HP Options Trial is a pragmatic, parallel type 3 effectiveness–implementation randomized trial comparing 3 optimized strategies for delivering 3HP—facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between DOT and SAT using a shared decision-making aid—to people receiving care at a large urban HIV clinic in Kampala, Uganda. Participants and healthcare providers were not blinded to arm assignment due to the nature of the 3HP delivery strategies. We conducted an interim analysis of participants who were enrolled and exited the 3HP treatment period between July 13, 2020 and April 30, 2021. The primary outcome, which was aggregated across trial arms for this interim analysis, was the proportion who accepted and completed 3HP (≥11 of 12 doses within 16 weeks of randomization). We used Bayesian inference analysis to estimate the posterior probability that this proportion would exceed 80% under at least 1 of the 3HP delivery strategies, a coprimary hypothesis of the trial. Through April 2021, 684 participants have been enrolled, and 479 (70%) have exited the treatment period. Of these 479 participants, 309 (65%) were women, mean age was 41.9 years (standard deviation (SD): 9.2), and mean time on antiretroviral therapy (ART) was 7.8 years (SD: 4.3). In total, 445 of them (92.9%, 95% confidence interval (CI): [90.2 to 94.9]) accepted and completed 3HP treatment. There were no differences in treatment acceptance and completion by sex, age, or time on ART. Treatment was discontinued due to a documented adverse event (AE) in 8 (1.7%) patients. The probability that treatment acceptance and completion exceeds 80% under at least 1 of the three 3HP delivery strategies was greater than 99%. The main limitations are that the trial was conducted at a single site, and the interim analysis focused on aggregate outcome data to maintain blinding of investigators to arm-specific outcomes. Conclusions The 3HP was widely accepted by people living with HIV (PLHIV) in Uganda, and very high levels of treatment completion were achieved in a programmatic setting. These findings show that 3HP can enable effective scale-up of tuberculosis preventive therapy (TPT) in high-burden countries, particularly when delivery strategies are tailored to target known barriers to treatment completion. Trial registration ClinicalTrials.gov NCT03934931.


2021 ◽  
pp. emermed-2021-211253
Author(s):  
Mariana Cannellotto ◽  
Mariano Duarte ◽  
Guillermo Keller ◽  
Ramiro Larrea ◽  
Eleonora Cunto ◽  
...  

BackgroundHyperbaric oxygen (HBO2) therapy has been proposed to treat hypoxaemia and reduce inflammation in COVID-19. Our objective was to analyse safety and efficacy of HBO2 in treatment of hypoxaemia in patients with COVID-19 and evaluate time to hypoxaemia correction.MethodsThis was a multicentre, open-label randomised controlled trial conducted in Buenos Aires, Argentina, between July and November 2020. Patients with COVID-19 and severe hypoxaemia (SpO2 ≤90% despite oxygen supplementation) were assigned to receive either HBO2 treatment or the standard treatment for respiratory symptoms for 7 days. HBO2 treatment was planned for ≥5 sessions (1 /day) for 90 min at 1.45 atmosphere absolute (ATA). Outcomes were time to normalise oxygen requirement to SpO2 ≥93%, need for mechanical respiratory assistance, development of acute respiratory distress syndrome and mortality within 30 days. A sample size of 80 patients was estimated, with a planned interim analysis after determining outcomes on 50% of patients.ResultsThe trial was stopped after the interim analysis. 40 patients were randomised, 20 in each group, age was 55.2±9.2 years. At admission, frequent symptoms were dyspnoea, fever and odynophagia; SpO2 was 85.1%±4.3% for the whole group. Patients in the treatment group received an average of 6.2±1.2 HBO2 sessions. Time to correct hypoxaemia was shorter in treatment group versus control group; median 3 days (IQR 1.0–4.5) versus median 9 days (IQR 5.5–12.5), respectively (p<0.010). OR for recovery from hypoxaemia in the HBO2 group at day 3 compared with the control group was 23.2 (95% CI 1.6 to 329.6; p=0.001) Treatment had no statistically significant effect on acute respiratory distress syndrome, mechanical ventilation or death within 30 days after admission.ConclusionOur findings support the safety and efficacy of HBO2 in the treatment of COVID-19 and severe hypoxaemia.Trial registration numberNCT04477954.


2021 ◽  
pp. 1-9
Author(s):  
Kavita Khoiwal ◽  
Anchal Agarwal ◽  
Amrita Gaurav ◽  
Ranjeeta Kumari ◽  
Anmol Mittal ◽  
...  

2021 ◽  
Author(s):  
Jason Gotlib ◽  
Andreas Reiter ◽  
Deepti H. Radia ◽  
Michael W. Deininger ◽  
Tracy I. George ◽  
...  

AbstractAdvanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase 2 trial (no. NCT03580655) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200 mg in patients with AdvSM (n = 62). The primary endpoint was overall response rate (ORR). Secondary endpoints included mean baseline change in AdvSM–Symptom Assessment Form Total Symptom Score and quality of life, time to response, duration of response, progression-free survival, overall survival, changes in measures of disease burden and safety. The primary endpoint was successfully met (P = 1.6 × 10-9), with an ORR of 75% (95% confidence interval 57–89) in 32 response-evaluable patients with AdvSM who had sufficient follow-up for response assessment, including 19% with complete remission with full or partial hematologic recovery. Reductions of ≥50% from baseline in serum tryptase (93%), bone marrow mast cells (88%) and KIT D816V variant allele fraction (60%) were observed. The most frequent grade ≥3 adverse events were neutropenia (24%), thrombocytopenia (16%) and anemia (16%). Avapritinib demonstrated a high rate of clinical, morphological and molecular responses and was generally well tolerated in patients with AdvSM.


2021 ◽  
Author(s):  
Kayla E. Hanson ◽  
Kristin Goddard ◽  
Ned Lewis ◽  
Bruce Fireman ◽  
Tanya R. Myers ◽  
...  

AbstractImportancePost-authorization monitoring of vaccines in a large population can detect rare adverse events not identified in clinical trials including Guillain-Barré syndrome (GBS). GBS has a background rate of 1-2 per 100,000 person-years.ObjectiveTo 1) describe cases and incidence of GBS following COVID-19 vaccination, and 2) assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines.DesignInterim analysis of surveillance data from the Vaccine Safety Datalink.SettingEight participating integrated healthcare systems in the United States.Participants10,158,003 individuals aged ≥12 years.ExposuresReceipt of Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine.Main Outcomes and MeasuresGBS with symptom onset in the 1-84 days after vaccination as confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared to the background rate, rate ratios (RRs) comparing GBS incidence in the 1-21 vs. 22-42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs. mRNA vaccination, using Poisson regression adjusted for age, sex, race/ethnicity, site, and calendar day.ResultsFrom December 13, 2020 through November 13, 2021, 14,723,318 doses of COVID-19 vaccines were administered, including 467,126 Ad.26.COV2.S, 8,573,823 BNT162b2, and 5,682,369 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of confirmed cases of GBS per 100,000 person-years in the 1-21 days after Ad.26.COV2.S was 34.6 (95% confidence interval [CI]: 15.8-65.7), significantly higher than the background rate, and the adjusted RR in the 1-21 vs. 22-42 days following Ad.26.COV2.S was 6.03 (95% CI: 0.79-147.79). Thirty-four cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate of confirmed cases per 100,000 person-years in the 1-21 days after mRNA vaccines was 1.4 (95% CI: 0.7-2.5) and the adjusted RR in the 1-21 vs. 22-42 days following mRNA vaccines was 0.56 (95% CI: 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs. mRNA vaccines, the adjusted RR was 20.56 (95% CI: 6.94-64.66).Conclusions and RelevanceIn this interim analysis of surveillance data of COVID-19 vaccines, the incidence of GBS was elevated after Ad.26.COV2.S. Surveillance is ongoing.


Sign in / Sign up

Export Citation Format

Share Document