NCT04771000

A Study of Micro Dose Ambrisentan in Hospitalized Patients With Respiratory Insufficiency Due to COVID-19

A Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Ambrisentan in Patients With Severe COVID-19

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 88 (actual)
• Sponsor: Noorik Biopharmaceuticals AG · Industry
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

Patients with COVID-19 frequently develop lower respiratory complications. Difficulty breathing and a low concentration of oxygen in the blood are of concern in patients with COVID-19, as they indicate that the lungs may be significantly affected. In some patients, respiratory symptoms may progress to the point where oxygen support is needed (i.e. use of an oxygen prongs, mask or ventilator). The exact mechanism of why patients with COVID-19 develop low concentrations of oxygen in blood is not fully understood. Some data suggest that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus Disease 2019 (COVID-19), can affect the body's blood vessels directly and extensively. In the lung, blood vessels participate in the absorption of oxygen. Endothelin is a potent hormone produced by human blood vessels. When increased, endothelin can result in the narrowing of blood vessels in the lung and decrease the volume of blood flowing through the lungs. This decrease in in blood flow through the lungs may be one of many factors affecting normal lung function. Ambrisentan can block the effects of endothelin in the body, and this could theoretically improve blood flow through the lungs. This study will evaluate whether ambrisentan, by blocking the effects of the hormone endothelin in the lungs, improves the breathing capacity of patients with COVID-19, increases the concentration of oxygen in the blood and prevents the progression to respiratory failure and death. Ambrisentan is a drug that is currently used to treat patients with pulmonary hypertension, a disease where blood flow through the lungs is decreased. Subjects participating in this study are those patients hospitalised with severe respiratory symptoms related to COVID-19, and are considered to be at high-risk of developing respiratory complications. Ambrisentan will be administered in the hospital, and will be continued at home for up to 28 days. In this study, ambrisentan will be administered at much lower doses that those used in patients with pulmonary hypertension.

Detailed description

This is a randomized, double-blind, placebo-controlled, multi-centre trial to evaluate the safety and efficacy of ambrisentan for the treatment of severe COVID-19. The population consists of hospitalized subjects who have a confirmed SARS-CoV-2 (a coronavirus (CoV) ) infection, are at high-risk of progression to respiratory failure or death and have low oxygen saturation and/or require oxygen supplementation at the time of admission. Pregnant or lactating women will not be allowed to participate in this study given the teratogenic potential of ambrisentan. Subjects requiring mechanical ventilation or intubation at the time of enrolment are considered to have respiratory failure and will not be allowed into the study, as one primary objective of the study is to evaluate the effect of ambrisentan in preventing respiratory failure. Enrolled subjects will be randomly assigned to the treatment arm or control arm at a 1:1 ratio. In the treatment arm, subjects will receive ambrisentan on top of the standard-of-care. In the control arm, subjects will receive the administration vehicle only (i.e., placebo) and on top of the standard of care. The study medication (ambrisentan or placebo) will be administered for up to 28 days. In the event that the subject is discharged between Day 4 and Day 28, the subject will continue the study treatment at home until completion of the 28-day study medication regimen. Investigators, the Sponsor and the subject will be blinded to the treatment assignment. A Drug Safety Monitoring Board will be monitoring the safety of the study.

Conditions

• Covid19
• Hypoxemia

Interventions

Type	Name	Description
DRUG	Ambrisentan	Endothelin receptor antagonist
DRUG	Placebo	Placebo

Timeline

• Start date: 2021-02-08
• Primary completion: 2023-02-27
• Completion: 2023-02-27
• First posted: 2021-02-25
• Last updated: 2023-03-21

Locations

13 sites across 2 countries: Croatia, Spain