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

Phase 2
Completed
Conditions
Covid19
Interventions
Registration Number
NCT05010876
Lead Sponsor
GCS Ramsay Santé pour l'Enseignement et la Recherche
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
44
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
standard care + C1 inhibitorPlaceboThe 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.
standard care + Icatibant + C1 inhibitorIcatibant InjectionThe 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.
standard care + placeboPlacebo-
standard care + C1 inhibitorC1 Inhibitor HumanThe 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.
standard care + Icatibant + C1 inhibitorC1 Inhibitor HumanThe 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.
Primary Outcome Measures
NameTimeMethod
Efficacy evaluation respiratory discomfort96 hours after the administration of treatment

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

Efficacy evaluation heart rate between 60 and 90 /min96 hours after the administration of treatment

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

Efficacy evaluation respiratory rate less than 20/min96 hours after the administration of treatment

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

Efficacy evaluation O2 saturation greater than 94% without oxygen supply96 hours after the administration of treatment

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

Secondary Outcome Measures
NameTimeMethod
Tolerance evaluationDay 10

The tolerance of the study products will be assessed by collecting adverse events that occurred during the study period.

Trial Locations

Locations (1)

Hôpital Privé de Parly II

🇫🇷

Le Chesnay, France

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