Pilot Study of Single Dose Bevacizumab as Treatment for Acute Respiratory Distress Syndrome (ARDS) in COVID-19 Patients

Phase 2TerminatedNCT04954014

Maimónides Biomedical Research Institute of Córdoba21 enrolled

Overview

Our hypothesis is that treating ARDS caused by COVID-19 with bevacizumab improves mortality. This is a phase II, multi-centered, randomized, open label, two-armed clinical trial to study the safety and efficacy of bevacizumab in COVID-19 positive patients who consequently developed ARDS (acute respiratory distress syndrome) and who have previously received anti-viral and anti-inflammatory treatment.

The vascular endothelial growth factor (VEGF) improves vascular capillarity, which plays an important role in the uncontrolled inflammatory reaction that happens in ARDS. As opposed to this event, angiogenic therapy (like bevacizumab) is known to contribute to normal vascularization, relevant for regaining vascular permeability. Studies in animal models have shown that treating ARDS with anti-VEGF therapy is effective.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

ARDS, Human Coronavirus Infection

Interventions

BevacizumabDRUG

Patients will receive best available treatment (BAT) for COVID-19 plus a single dose of bevacizumab calculated as 7,5 mg/kg diluted in 250cc of saline solution during 90 minutes.

BATDRUG

Patients will receive best available treatment for COVID-19.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age equal or over 18 and under 90 years old. * Confirmed COVID-19 positive diagnostic through PCR. * Radiological image compatible with non-cardiogenic bilateral pleuropulmonary exudate. * Patient has received anti-viral and anti-inflammatory therapy. * Present any of the following clinical-functional criteria: 1. Respiratory distress: Tachypnea\> 30 breaths / minute 2. Partial arterial oxygen pressure (PaO2) / Fraction of inspiration (FiO2) ≤ 300 mmHg * Signed informed consent, directly or delegated. Exclusion Criteria: * Severe liver dysfunction (Child Pugh ≥ 3 or AST\> 5 times normal) * Severe renal dysfunction with glomerular filtration \<30 mL / minute or under treatment with hemodialysis or peritoneal dialysis. * Poorly controlled hypertension (BPs\> 160 mmHg or TAd \<100 mmHg) or having a history previous hypertensive crisis or hypertensive encephalopathy. * History of poorly controlled heart disease with a NYHA\> 2. * History of thrombosis in the previous 6 months. * Signs of active bleeding. * Open wounds, gastrointestinal perforation. * Diagnosis of thrombophilic diseases or hemorrhagic diathesis. * Active viral hepatitis or HIV not properly treated. * Intolerance or allergy to bevacizumab or its components. * Pregnancy.

Locations (1)

Hospital Universitario Reina Sofía

Córdoba, Córdona, Spain

Outcomes

Primary Outcomes

Mortality

Time frame: After 28 days

Secondary Outcomes

PaO2/FiO2

Ratio calculation

Time frame: 6 hours before bevacizumab administration and 24 hours,72 hours,7 days,14 days and 28 days after.

Clinical improvement according to scale recommended by WHO for COVID19

Clinical improvement according to WHO scale (World Health Organization) for COVID19 which goes from 1 to 7 points.

Time frame: 24 hours, 72 hours, 7 days, 14 days and 28 days after treatment.

Time to clinical improvement as stated in the National Early Warning Score 2 (NEWS)

NEWS assesses clinical risk on a scale of 1 (low) to 8 (high)

Time frame: From randomization until improvement of 2 points in the scale or until hospital discharge, whatever happens first, assessed up to 28 days.

Time to improvement of oxygenation

Improvement shown during, at least, 48 hours.

Time frame: From randomization until outcome event assessed up to 28 days.

Time to improvement of Sp2/O2 ratio regarding the worst Sp2/O2 ratio obtained before bevacizumab treatment.

Time to improvement of Sp2/O2 ratio regarding the worst Sp2/O2 ratio obtained before bevacizumab treatment

Time frame: From randomization until first documented Sp2/O2 ratio improvement, assessed up to 28 days.

Time to absence of oxygen need to maintain a saturation equal or over 93%

Data from ClinicalTrials.gov

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