Evaluation of the Effects of Bradykinin Antagonists on Pulmonary Manifestations of COVID-19 Infections (AntagoBrad-Cov Study).

NCT ID: NCT05010876

Last Updated: 2022-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-04
• Study Completion Date: 2021-06-21

Brief Summary

The main objective of this study is to evaluate the efficacy of human C1 inhibitor, administered alone or in combination with icatibant (a specific bradykinin B2 receptor antagonist) on the pulmonary manifestations of COVID-19 infections.

Detailed Description

Prospective, prospective, multicentre, double-blind, randomised, multi-centre study of three parallel groups of patients:

• Group 1 (n=15): standard of care + C1 inhibitor
• Group 2 (n=15): standard care + icatibant + C1 inhibitor
• Group 3 (n=15): standard support + placebo

The study has two parts:

• A 4-day (96-hour) therapeutic part during which the patient will be evaluated nine times (H0, H4, H12, H24, H36, H48, H60, H72 and H96).
• A follow-up part of 6 days with at least two assessments (D7 and D10).

The maximum duration of patient participation in the study will be 10 days.

Conditions

Covid19

Study Design

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

Study Groups

standard care + C1 inhibitor

The C1 inhibitor will be used at a dose of 1000 units per slow infusion (two hours). Two infusions will be given 24 hours apart. These doses correspond to the usual doses used in the treatment of conditions in which the C1-Inhibitor is indicated.

Group Type: EXPERIMENTAL

C1 Inhibitor Human

Intervention Type: DRUG

standard care + 1000 units of C1 inhibitor during 2 slow infusions of 500 units

Placebo

Intervention Type: OTHER

The placebo will be physiological serum presented in forms mimicking the C1-Inhibitor and the icatibant.

standard care + Icatibant + C1 inhibitor

The C1 inhibitor will be used at a dose of 1000 units per slow infusion (two hours). Two infusions will be given 24 hours apart. These doses correspond to the usual doses used in the treatment of conditions in which the C1-Inhibitor is indicated.

The icatibant will be used in a single injection of 30 mg subcutaneously, preferably in the abdominal region. These doses correspond to the doses usually used in the treatment of conditions in which icatibant is indicated.

Group Type: EXPERIMENTAL

C1 Inhibitor Human

Intervention Type: DRUG

standard care + 1000 units of C1 inhibitor during 2 slow infusions of 500 units

Icatibant Injection

Intervention Type: DRUG

a single injection of 30 mg subcutaneously

standard care + placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

The placebo will be physiological serum presented in forms mimicking the C1-Inhibitor and the icatibant.

Interventions

C1 Inhibitor Human

standard care + 1000 units of C1 inhibitor during 2 slow infusions of 500 units

Intervention Type: DRUG

Icatibant Injection

a single injection of 30 mg subcutaneously

Intervention Type: DRUG

Placebo

The placebo will be physiological serum presented in forms mimicking the C1-Inhibitor and the icatibant.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patient over 18 years of age, having read and signed the consent form for participation in the study after the reflection period (≤ 15 minutes)
• Patient screened for COVID+ by RT-PCR on nasopharyngeal swab
• Patient with at least three of the following respiratory signs:

• Temperature >38° C
• Non-productive dry cough
• Presence of crackling rales on auscultation
• Respiratory discomfort felt by the patient
• Heart rate > 90/min
• Respiratory rate >20/min
• O2 saturation ≤ 93%
• Patient whose clinical condition, in the opinion of the investigator, requires hospital monitoring.
• Patient who would have been monitored and treated outside of study participation, including prevention of thromboembolic risk with LMWH.

Exclusion Criteria

• Patient with pre-existing respiratory disease (cancer, COPD, asthma, emphysema) or smoking history of > 25 years)
• Patient with a known allergy to one of the study products
• Patient treated with anti TNF, IL1 or IL6
• Patient requiring immediate intubation
• Patient on a low sodium diet
• Patient under protective custody, guardianship or trusteeship
• Patient not affiliated to the French social security system
• Patient participating in another therapeutic protocol
• Pregnant or likely to become pregnant (woman of childbearing age without effective contraception and without HCG dosage)
• Patient unable to understand informed information and/or give written informed consent: dementia, psychosis, consciousness disorders, non-French speaking patient

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GCS Ramsay Santé pour l'Enseignement et la Recherche

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denis VINCENT, MD PD

Role: STUDY_DIRECTOR

Médecine interne, Faculté de Montpellier

Locations

Hôpital Privé de Parly II

Le Chesnay, , France

Countries

France

Other Identifiers

2020-002225-29

Identifier Type: -

Identifier Source: org_study_id