CONNECTS Master Protocol for Clinical Trials Targeting Macro-, Micro-immuno-thrombosis, Vascular Hyperinflammation, and Hypercoagulability and Renin-angiotensin-aldosterone System (RAAS) in Hospitalized Patients With COVID-19 (ACTIV-4 Host Tissue)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,060
- 试验地点
- 51
- 主要终点
- Oxygen Free Days Through Day 28.
研究概览
简要总结
The overarching goal of the Master Protocol is to find effective strategies for inpatient management of patients with COVID-19. Therapeutic goals for patients hospitalized for COVID-19 include hastening recovery and preventing progression to critical illness, multiorgan failure, or death. Our objective is to determine whether modulating the host tissue response improves clinical outcomes among patients with COVID-19. The primary analysis will include data from NCT05593770.
详细描述
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. The clinical spectrum of COVID-19 infection is broad, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and death. Between 13 and 40% of patients become hospitalized, up to 30% of those hospitalized require admission for intensive care, and there is a 13% inpatient mortality rate. The reasons for hospitalization include respiratory support, as well as support for failure of other organs, including the heart and kidneys. The risk of thrombotic complications is increased, even when compared to other viral respiratory illnesses, such as influenza. While 82% of hospitalized patients with COVID-19 are ultimately discharged alive, median length of stay is 10-13 days.
Early work in treating COVID-19 has focused on preventing worsening of the initial clinical presentation to prevent hospitalization and disease progression to organ failure and death. Studies conducted under this Master Host Tissue Protocol are expected to extend our knowledge of how to manage patients who are hospitalized for COVID-19 illness. Our objective is to determine whether modulating the host tissue response improves clinical outcomes among patients with COVID-19. This Master Protocol is a randomized, placebo-controlled trial of agents targeting the host response in COVID-19 in hospitalized patients with hypoxemia. The Master Host Tissue Protocol is designed to be flexible in the number of study arms, the use of a single placebo group, and the stopping and adding of new therapies. Our primary outcome is oxygen free days through day 28. This is defined as days alive and without supplemental oxygen use during the first 28 days following randomization. Patients who die on or before day 28 are assigned -1 oxygen free days.
April 20, 2022 TRV027 and TXA127 arms closed to accrual.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Which study drug arm the participant enters will be known to the research sites and the participants, but assignment to active versus placebo will be blinded. The randomized assignment, concealed from the research team, will be transmitted to the site pharmacy, who will provide study medication. The participant, treating clinicians, study personnel (other than the unblinded statistician who will prepare closed DSMB interim reports), and outcome assessors will all remain blinded to group assignment until after the database is locked and blinded analysis is completed.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
TXA127 (4/20/2022 Arm Closed to Accrual)
An investigational peptide agonist of Mas receptors.
干预措施: TXA127 (Drug)
TRV027 (4/20/2022 Arm Closed to Accrual)
An investigational peptide biased agonist of the AT1 receptor.
干预措施: TRV027 (Drug)
Placebo
NaCl 0.9% infused to match the duration of the agent for TXA127, TRV027, and APN01.
Orange film-coated, plain, bioconvex tablets for fostamatinib.
For the purposes of interim and final analyses, the route and frequency of placebo will be ignored, and all placebo participants will be pooled together as a single group. In comparing an active drug versus placebo, only those placebo participants that were eligible for the active drug will be included.
干预措施: Placebo (Drug)
Fostamatinib
An investigational oral spleen tyrosine kinase inhibitor.
干预措施: Fostamatinib (Drug)
结局指标
主要结局
Oxygen Free Days Through Day 28.
时间窗: Day 1 to Day 28
This is defined as days alive and without supplemental oxygen use during the first 28 days following randomization. Patients who die on or before day 28 are assigned -1 oxygen free days. Patients will be considered to be receiving supplemental oxygen therapy when they are receiving any of the following: supplemental oxygen by nasal cannula, supplemental oxygen by face mask, high flow nasal cannula (HFNC), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).
次要结局
- Clinical Status Assessed Using WHO 8-point Ordinal Scale at Day 60(Day 60)
- Ventilator-free Days Through Day 28(Day 1 to Day 28)
- Hospital-free Days Through Day 28(Day 1 to Day 28)
- Respiratory Failure-free Days Through Day 28(Day 1 to Day 28)
- In-hospital Mortality(Day 1 to hospital discharge or Day 90 whichever comes first)
- Alive and Oxygen Free at Day 14(Day 1 to Day 14)
- Alive and Oxygen Free at Day 28(Day 1 to Day 28)
- Alive and Free of New Invasive Mechanical Ventilation at Day 28(Day 1 to Day 28)
- 28-day Mortality(Day 28)
- 60-day Mortality(Day 60)
- 90-day Mortality(Day 90)
- Clinical Status Assessed Using World Health Organization(WHO) 8-point Ordinal Scale(Day 14)
- Clinical Status Assessed Using WHO 8-point Ordinal Scale at Day 28(Day 28)
研究者
Sean Collins
Professor, Emergency Medicine
Vanderbilt University Medical Center