RESUMO
Background: Effective therapeutics for severe acute respiratory syndrome CoronaVirus-2 (SARS-CoV-2) infection are evolving. Under Emergency Use Authorization, COVID-19 convalescent plasma (CCP) was widely used in individuals hospitalized for COVID-19, but few randomized controlled trials supported its efficacy to limit respiratory failure or death. Methods: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1) was a double-blind, multi-site, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of CCP with conventional therapy in hospitalized Veterans with SARS-CoV-2 infection and early respiratory compromise (requirement for oxygen). Participants (planned sample size 702) were randomized 1:1 to receive CCP with high titer neutralizing activity or 0.9% saline, stratified by site and age (≥65 versus <65 years old). Participants were followed daily during initial hospitalization and at Days 15, 22 and 28. Outcomes: The composite primary outcome was acute hypoxemic respiratory failure or all-cause death by Day 28. Secondary outcomes by day 28 included time-to-recovery, clinical severity, mortality, rehospitalization for COVID-19, and adverse events. Serial respiratory and blood samples were collected for safety, virologic and immunologic analyses and future studies. Key variables in predicting the success of CURES-1 were: (1) enrollment early in the course of severe infection; (2) use of plasma with high neutralizing activity; (3) reliance on unambiguous, clinically meaningful outcomes. CURES-1 was terminated for futility due to perceived inability to enroll in the lull between the Alpha and Delta waves of the SARS CoV-2 epidemic. Conclusions: VA CURES-1 was a large multi-site trial designed to provide conclusive information about the efficacy of CCP in well-characterized patients at risk for progression of COVID-19. It utilized a rigorous study design with relevant initial timing, quality of product and outcomes. Trial registration: ClinicalTrials.gov Identifier: NCT04539275.
RESUMO
BACKGROUND: Chronic low back pain (cLBP) is a common and highly disabling problem world-wide. Although many treatment options exist, it is unclear how to best sequence the multitude of care options to provide the greatest benefit to patients. METHODS: The Sequential and Comparative Evaluation of Pain Treatment Effectiveness Response (SCEPTER) trial uses a pragmatic, randomized, stepped design. Enrollment targets 2529 participants from 20 Veterans Affairs (VA) medical centers. Participants with chronic low back pain will first be randomized to one of three options: 1) an internet-based self-management program (Pain EASE); 2) a tailored physical therapy program (Enhanced PT); or 3) continued care with active monitoring (CCAM), a form of usual care. Participants not achieving a 30% or 2-point reduction on the study's primary outcome (Brief Pain Inventory Pain Interference (BPI-PI) subscale), 3 months after beginning treatment may undergo re-randomization in a second step to cognitive behavioral therapy for chronic pain, spinal manipulation therapy, or yoga. Secondary outcomes include pain intensity, back pain-related disability, depression, and others. Participants will be assessed every three months until 12 months after initiating their final trial therapy. Companion economic and implementation analyses are also planned. RESULTS: The SCEPTER trial is currently recruiting and enrolling participants. CONCLUSIONS: Trial results will inform treatment decisions for the stepped management of chronic low back pain - a common and disabling condition. Additional analyses will help tailor treatment selection to individual patient characteristics, promote efficient resource use, and identify implementation barriers of interventions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT04142177.
