A randomized, open-label, adaptive, proof-of-concept clinical trial of modulation of host thromboinflammatory response in patients with COVID-19.

Phase 1

• Conditions: COVID-19; MedDRA version: 20.0Level: LLTClassification code 10038700Term: Respiratory infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2020-001739-28-BE
• Lead Sponsor: ZLeuven

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-10
• Last Update Posted: 18 August 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 210

Inclusion Criteria

1. Subject (=18 years old) or legally authorized representative provides informed consent prior to initiation of any study procedures. When signed informed consent is not possible (e.g. due to restrictions to prevent viral transmission), verbal informed consent in the presence of a witness will be obtained and documented in the medical files. Signed informed consent will be obtained as soon as the safety concerns are mitigated.

2. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.

3. Male or non-pregnant female adult =18 years of age at time of enrolment.

4. Has a confirmed diagnosis of SARS-CoV-2 infection, defined as either:
a. laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen as diagnosed within 72 hours prior to randomization
or
b. The combination of upper or lower respiratory infection symptoms (fever, cough, dyspnea, desaturation) and typical findings on chest CT scan and absence of other plausible diagnoses

5. Illness of any duration, and at least one of the following:
a. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), or
b. Clinical assessment (evidence of rales/crackles on lung auscultation) AND SpO2 = 94% on room air, or
c. Requiring mechanical ventilation and/or supplemental oxygen.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 105
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 105

Exclusion Criteria

1. ALT/AST > 8 times the upper limit of normal.

2. Pregnancy or breastfeeding.

3. Allergy to any study medication.

4. Any medical condition which would impose an unacceptable safety hazard by participation in the study.

5. Study drug-specific exclusion criteria:

• For Aprotinin:
o Known active thromboembolic disease, defined as a history of idiopathic (unprovoked) deep vein thrombosis or pulmonary embolism, recent (<3m) deep vein thrombosis or pulmonary embolism, recent (<6m) myocardial infarction or coronary stenting, recent (<6m) ischemic stroke
o Renal insufficiency with CrCl <30ml/min or continuous renal replacement therapy, hemodialysis, or peritoneal dialysis
o Recent (<6m) cardiac surgery with cardiopulmonary bypass and/or use of aprotinin

• For LMWH:
o Active bleeding, a history of intracranial bleeding, or a recent (<3m) GI bleeding requiring transfusion and/or intervention, recent surgery in the central nervous system
o Renal insufficiency with CrCl < 20ml/min or continuous renal replacement therapy, hemodialysis, or peritoneal dialysis
o Blood platelet count < 30 000/µL
o Other conditions that are judged to carry an increased risk of bleeding as judged by the investigator
o Need for therapeutic anticoagulation (known active thrombo-embolic diseases, atrial fibrillation, mechanical prosthetic heart valve,…)

• For Anakinra:
o Impairment of cardiac function defined as severe heart failure, unstable angina pectoris, myocardial infarction within 6 months before enrollment, ventricular arrhythmia requiring treatment or intervention.
o Severe renal dysfunction (creatinine clearance = 20mL/min) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
o Uncontrolled hypertension (persistent systolic blood pressure >180mmHg, or diastolic blood pressure >110mmHg)
o Clinical suspicion of latent tuberculosis
o Clinical suspicion of severe bacterial surinfection (e.g. ventilator-associated pneumonia)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified