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

NCT05010876 | Completed Phase 2

• 1 other identifier: 2020-002225-29
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19

Outcome Measures

Primary Outcomes (4)

• Efficacy evaluation respiratory discomfort

  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. The evaluation of the treatment efficacy of the study is based on the clinical monitoring of the patient and particularly on the following combination of criteria as experienced by the patient : * no respiratory discomfort * heart rate between 60 and 90 /min * respiratory rate less than 20/min * O2 saturation greater than 94% without oxygen supply

  96 hours after the administration of treatment

• Efficacy evaluation heart rate between 60 and 90 /min

  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. The evaluation of the treatment efficacy of the study is based on the clinical monitoring of the patient and particularly on the following combination of criteria as experienced by the patient : * no respiratory discomfort * heart rate between 60 and 90 /min * respiratory rate less than 20/min * O2 saturation greater than 94% without oxygen supply

  96 hours after the administration of treatment

• Efficacy evaluation respiratory rate less than 20/min

  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. The evaluation of the treatment efficacy of the study is based on the clinical monitoring of the patient and particularly on the following combination of criteria as experienced by the patient : * no respiratory discomfort * heart rate between 60 and 90 /min * respiratory rate less than 20/min * O2 saturation greater than 94% without oxygen supply

  96 hours after the administration of treatment

• Efficacy evaluation O2 saturation greater than 94% without oxygen supply

  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. The evaluation of the treatment efficacy of the study is based on the clinical monitoring of the patient and particularly on the following combination of criteria as experienced by the patient : * no respiratory discomfort * heart rate between 60 and 90 /min * respiratory rate less than 20/min * O2 saturation greater than 94% without oxygen supply

  96 hours after the administration of treatment

Secondary Outcomes (1)

• Tolerance evaluation

  Day 10

Study Arms (3)

standard care + C1 inhibitor

EXPERIMENTAL

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.

Drug: C1 Inhibitor Human; Other: Placebo

standard care + Icatibant + C1 inhibitor

EXPERIMENTAL

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.

Drug: C1 Inhibitor Human; Drug: Icatibant Injection

standard care + placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

C1 Inhibitor Human DRUG

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

standard care + C1 inhibitor; standard care + Icatibant + C1 inhibitor

Icatibant Injection DRUG

a single injection of 30 mg subcutaneously

standard care + Icatibant + C1 inhibitor

Placebo OTHER

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

standard care + C1 inhibitor; standard care + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GCS Ramsay Santé pour l'Enseignement et la Recherche: lead

Study Sites (1)

Hôpital Privé de Parly II

Le Chesnay, 78150, France

Location

MeSH Terms

Conditions

COVID-19

Interventions

Complement C1 Inhibitor Protein; icatibant

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins

Study Officials

• Denis VINCENT, MD PD

  Médecine interne, Faculté de Montpellier

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, double-blind, multicentre, prospective study of three parallel groups of patients.

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: August 18, 2021
• Study Start: February 4, 2021
• Primary Completion: June 13, 2021
• Study Completion: June 21, 2021
• Last Updated: December 22, 2022

Record last verified: 2021-08

Locations

FR (1)