General public

What is ACTIV-4 Host Tissue?

In response to the global COVID-19 pandemic, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private initiative was organized by NIH and the Foundation for the NIH (FNIH). ACTIV developed an international strategy for an integrated research response to COVID-19 by evaluating and prioritizing promising candidates for COVID-19 treatment.

ACTIV-4 Host Tissue aims to find effective strategies for patients hospitalized with COVID-19 by impacting the Renin-Angiotensin-Aldosterone System (RAAS), which has been directly implicated in the development of acute respiratory distress syndrome (ARDS).

Who can be in this study?

COVID-positive adults admitted to the hospital requiring supplemental oxygen may be eligible for this study. Only hospitals that are registered for recruitment can enroll subjects.

What Happens in this study?

• Information will be collected from study participants’ medical records and by asking them questions during the time they are in the hospital.
• Participants will either receive a study medication or be treated as usual by their doctors. Assignment is determined by random chance, like the flip of a coin. Neither participants nor their doctors will know what assignment they receive.
• Some additional blood tests may be performed
• Participants will be contacted after they leave the hospital to see how they and doing and feeling.

Who is paying for this study?

The National Heart, Lung and Blood Institute (NHLBI), which is part of the U.S. government, is paying for this research.

Trial Summary:

Purpose:

The study will evaluate the safety and efficacy of multiple investigational agents intended to enhance the host immune response to SARS-CoV-2 infection, or directly enhance viral control, in order to limit disease progression. Using a master protocol, successive trials within this protocol will be adaptive, randomized, and initially placebo controlled. All participants will receive standard of care (SOC) treatment. If an investigational agent shows superiority over placebo + SOC as initially defined, SOC for future investigational treatment evaluations will be modified accordingly. The initial investigational agents will be neutralizing monoclonal antibodies.

Study Design:

Multicenter, randomized, blinded, and placebo-controlled master protocol

Primary Objectives

To hasten recovery and prevent progression of critical illness in patients. We will assess this by looking at days without supplemental oxygen at 28 days after receiving study treatment.

Secondary Outcome Measures

• Organ dysfunction that may be associated with progression of COVID-19
• Mortality

Study Size:

This study will enroll 600 patients per treatment arm (divided between placebo and active agent).