Use of Angiotensin-(1-7) in COVID-19

NCT ID: NCT04633772

Last Updated: 2021-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-05
• Study Completion Date: 2021-11-01

Brief Summary

The renin-angiotensin system (RAS) has a relevant role in COVID-19, as the virus will enter host's cells via the angiotensin-converting enzyme 2 (ACE2); RAS disequilibrium might also play a key role in the modulation of the inflammatory response that characterizes the lung involvement. Angiotensin-(1-7) is a peptide that could be altered in COVID-19 patient and its supplementation may potentially helpful in this setting.

Detailed Description

A novel Coronavirus (SARS-CoV-2) described in late 2019 in Wuhan, China, has led to a pandemic and to a specific coronavirus-related disease (COVID-19), which is mainly characterized by a respiratory involvement. While researching for a vaccine has been started, effective therapeutic solutions are urgently needed to face this threaten. The renin-angiotensin system (RAS) has a relevant role in COVID-19, as the virus will enter host's cells via the angiotensin-converting enzyme 2 (ACE2); RAS disequilibrium might also play a key role in the modulation of the inflammatory response that characterizes the lung involvement. Angiotensin-(1-7) is a peptide that could be altered in COVID-19 patient and it may potentially improve respiratory function in this setting. This a randomized, controlled, investigator-initiated Phase I/Phase II trial is conceived to test the safety and the efficacy of intravenous angiotensin-(1-7) infusion in COVID-19 patients with severe pneumonia admitted to the intensive care unit (ICU). The first phase of the study, with a limited number of patients (n=30) will serve to confirm the safety of the intravenous infusion of the drug by observing the incidence of the adverse events (phase I, open label). In a second phase of the study, conducted in a double-blind manner and including a larger cohort of patients (n=100, Phase II), patients will be randomly assigned to receive either an Angiotensin-(1-7) infusion or placebo. The primary endpoint of the study will be the number of supplemental oxygen-free days by day 28. Secondary outcomes will include length of hospital stay, ICU and hospital free days, ICU and hospital mortality, need for mechanical ventilation, weaning time from mechanical ventilation if intubated, secondary infections, vasopressor needs, changes in PaO2 / FiO2, incidence of deep vein thrombosis, changes in inflammatory markers, plasma levels of angiotensin II and angiotensin (1-7) and radiological findings.

Conditions

Infection, Coronavirus; Respiratory Failure

Keywords

angiotensin-(1-7); ARDS; renin angiotensin system

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

NaCl 0.9%

Angiotensin-(1-7)

Group Type: EXPERIMENTAL

Angiotensin-(1-7)

Intervention Type: DRUG

Intravenous supplementation of Angiotensin-(1-7)

Interventions

Angiotensin-(1-7)

Intravenous supplementation of Angiotensin-(1-7)

Intervention Type: DRUG

Placebo

NaCl 0.9%

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Admission to the Intensive Care Unit with severe pneumonia criteria (clinical signs of pneumonia + one of the following criteria: respiratory rate greater than 30/minute; signs of respiratory effort, SatO2 < 90% in room air);
• COVID-19 confirmed or highly suspicious (positive contact or suggestive image)

Exclusion Criteria

• Diagnosed with cancer (at any stage);
• Hemodynamic instability (need for vasopressors);
• Pregnant women; Immunocompromised patients;
• Palliative Care;
• Inclusion in any other interventionist study;
• Heart failure as a predominant cause of acute respiratory failure;
• Decompensated liver cirrhosis;
• HIV +;
• Dialysis;
• Home / long-term oxygen therapy;
• Idiopathic pulmonary fibrosis

• Minimum Eligible Age: 17 Years
• Maximum Eligible Age: 81 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federal University of Minas Gerais

OTHER

Sponsor Role: collaborator

Angitec

UNKNOWN

Sponsor Role: collaborator

Fonds Erasme pour la Recherche Medicale

UNKNOWN

Sponsor Role: collaborator

Erasme University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robson AS Santos

Role: PRINCIPAL_INVESTIGATOR

Angitex

Ana Martins Valle

Role: PRINCIPAL_INVESTIGATOR

Federal University of Minas Gerais

Filippo Annoni

Role: PRINCIPAL_INVESTIGATOR

H.U.B Erasme

Locations

Hospital Eduardo de Menezes

Belo Horizonte, Minas Gerais, Brazil

Hospital Mater Dei

Belo Horizonte, Minas Gerais, Brazil

Countries

Brazil

References

Martins ALV, Annoni F, da Silva FA, Bolais-Ramos L, de Oliveira GC, Ribeiro RC, Diniz MML, Silva TGF, Pinheiro BD, Rodrigues NA, Dos Santos Matos AH, Motta-Santos D, Campagnole-Santos MJ, Verano-Braga T, Taccone FS, Santos RAS. Angiotensin-(1-7) infusion in COVID-19 patients admitted to the ICU: a seamless phase 1-2 randomized clinical trial. Ann Intensive Care. 2024 Sep 4;14(1):139. doi: 10.1186/s13613-024-01369-0.

Reference Type: DERIVED

PMID: 39231898 (View on PubMed)

Other Identifiers

RBR-35734p

Identifier Type: -

Identifier Source: org_study_id