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

GCS Ramsay Santé pour l'Enseignement et la Recherche

Status and phase: Completed; Phase 2

Conditions: Covid19

Treatments: Drug: Icatibant Injection; Other: Placebo; Drug: C1 Inhibitor Human

Study type: Interventional

Funder types: Other

Identifiers

NCT05010876

2020-002225-29

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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44 participants in 3 patient groups, including a placebo group

standard care + C1 inhibitor

Experimental group

Description:

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.

Treatment:

Drug: C1 Inhibitor Human

Other: Placebo

standard care + Icatibant + C1 inhibitor

Experimental group

Description:

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.

Treatment:

Drug: C1 Inhibitor Human

Drug: Icatibant Injection

standard care + placebo

Placebo Comparator group

Treatment:

Other: Placebo