The ACCORD clinical trials program brings together expertise of the Southampton National Institute for Health Research Biomedical Research Centre (NIHR BRC), NIHR Health Protection Research Unit for Emerging and Zoonotic Diseases, NIHR Respiratory Translational Research Collaboration, NIHR Southampton Clinical Trials Unit, pharmaceutical companies, IQVIA and the NIHR Clinical Research Facility (CRF) network to enable the rapid development, conduct and reporting of clinical trials of candidate agents for the treatment of COVID-19. There are currently no approved therapeutic agents available to treat coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of COVID-19 disease, and there is an urgent public health need for rapid development of such interventions.
This adaptive platform study is designed to rapidly assess multiple candidate agents as treatments for COVID-19. The master protocol outlines the overall structure of the study, including the population, inclusion and exclusion criteria, randomisation scheme, primary, secondary, and exploratory outcomes, study design, statistical methodology, and planned analyses that are common for all candidate agents to be tested. The master protocol is structured such that multiple candidate agents from different pharmaceutical companies can be evaluated simultaneously.
The plan is to add candidate agents as they are identified, and to remove therapies once they have completed their evaluation. The sub-protocols will outline the scientific rationale, eligibility, treatment schema, and other specifics for each candidate agent. Study centres will be located in the United Kingdom. Overall, it is estimated that approximately 12 centres and investigators will initially take part in the study. It is estimated that up to 1,800 patients will participate in the overall study.
There are no approved treatments or vaccines, and hence there is an urgent need to assess the efficacy/safety of antivirals and other therapeutics to treat coronavirus (COVID-19). The Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (INSIGHT-10), is a double-blind placebo-controlled trial, of the anti-viral, remdesivir, for the coronavirus (COVID-19) treatment in hospitalised adults. This randomised control trial is testing whether a daily intravenous infusion of remdesivir (active drug) compared to N-saline placebo, provides clinical benefit, and is safe.
The ILIAD-7 study's goal is to successfully trial CYT107 on COVID-19 patients as part of a global effort to treat the disease. IL-7 (CYT107) may prevent patients who are in the hospital for COVID-19 from progressing to having to be treated in the ICU. A Phase II randomized clinical trial is in the process of regulatory submission, building upon the prior and ongoing clinical trials of CYT107.
The REALIST trial is a trial of mesenchymal stromal cells (MSCs) for acute respiratory failure.
RECOVERY is a randomised trial among adults hospitalised for confirmed coronavirus (COVID-19). Eligible patients are randomly allocated between several treatment arms, each to be given in addition to the usual standard of care in the participating hospital: no additional treatment vs Lopinavir-Ritonavir vs Interferon β1b vs low-dose corticosteroids. For patients for whom not all the trial arms are appropriate or at locations where not all are available, randomisation will be between fewer arms.
The main outcomes will be in-hospital death, discharge, and need for ventilation. For the main analyses, follow-up will be censored at 28 days after admission. Additional information on longer term outcomes may be collected through review of medical records or linkage to medical databases such as those managed by NHS Digital and equivalent organisations in the devolved nations.
REMAP-CAP is an international platform trial that has been specifically designed for a pandemic period. The aim is to generate evidence that can be applied during the pandemic to reduce mortality, reduce intensive care use, and reduce morbidity in severely ill patients with coronavirus (COVID-19) infection. The platform will test multiple treatments at the same time (antivirals, immune modulation drugs and corticosteroids) and more treatments will be added as new evidence emerges. If a treatment is beneficial, more patients will be treated with that drug within the trial, improving outcomes and reducing ICU stays, even before the results are declared and the trial ends. It provides a type of self-learning healthcare system, which is important in this fast-moving pandemic.
While there are no current vaccines, prophylactic or therapeutic agents of proven efficacy for treating COVID-19, several medications licensed for patients with autoimmune disease can be used to prevent overactivation of the immune response in severe COVID-related disease. TACTIC is recruiting patients at an early stage in the disease course, aiming for a time point where the patient is experiencing infective symptoms and starting to show pulmonary complications. The purpose is to prevent organ damage and reduce the need to transfer to ICU and ventilation. The trial has two treatment arms and a comparator arm using the following drugs: baricitinib and ravulizumab.
TACTIC trial aims to currently randomise COVID-19 positive patients into three arms, two active and one comparator. Arm one and two consists of baricitinib and ravulizumab respectively. Arm three consists of standard of care alone. Subjects are treated with their assigned regime during 14 days. Depending on the drug regimen they are assigned to, patients will either have 14-day dosing (baricitinib) or a single dose (ravulizumab). After the treatment phase, patients will have a 28-day and three-month follow up. Patients will undergo blood testing as part of the routine care, and data relevant for the study will be taken from medical records whenever possible. Arms may be added or stopped depending on data and a recommendation from the independent data monitoring committee. The aim of this trial is to reduce the number of COVID-19 patients that will be admitted to ICU. Candidates: ravulizumab, baricitinib.