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

Sponsor

Maimónides Biomedical Research Institute of Córdoba (Other)

Overall Status

Terminated

CT.gov ID

NCT04954014

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
ARDS, Human Coronavirus Infection	Drug: Bevacizumab Drug: BAT	Phase 2

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 1, 2020

Actual Primary Completion Date :

Aug 31, 2021

Actual Study Completion Date :

Aug 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BEVACIZUMAB Patients will receive best available treatment (BAT) for COVID-19 plus single dose bevacizumab calculated as 7,5 mg/kg diluted in 250cc of saline solution during 90 minutes.	Drug: Bevacizumab 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.
Active Comparator: BEST AVAILABLE TREATMENT Patients will receive best available treatment for COVID-19.	Drug: BAT Patients will receive best available treatment for COVID-19.

Arm

Intervention/Treatment

Experimental: BEVACIZUMAB

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

Drug: Bevacizumab

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.

Active Comparator: BEST AVAILABLE TREATMENT

Patients will receive best available treatment for COVID-19.

Drug: BAT

Patients will receive best available treatment for COVID-19.

Outcome Measures

Primary Outcome Measures

Mortality [After 28 days]
Mortality

Secondary Outcome Measures

PaO2/FiO2 [6 hours before bevacizumab administration and 24 hours,72 hours,7 days,14 days and 28 days after.]
Ratio calculation
Clinical improvement according to scale recommended by WHO for COVID19 [24 hours, 72 hours, 7 days, 14 days and 28 days after treatment.]
Clinical improvement according to WHO scale (World Health Organization) for COVID19 which goes from 1 to 7 points.
Time to clinical improvement as stated in the National Early Warning Score 2 (NEWS) [From randomization until improvement of 2 points in the scale or until hospital discharge, whatever happens first, assessed up to 28 days.]
NEWS assesses clinical risk on a scale of 1 (low) to 8 (high)
Time to improvement of oxygenation [From randomization until outcome event assessed up to 28 days.]
Improvement shown during, at least, 48 hours.
Time to improvement of Sp2/O2 ratio regarding the worst Sp2/O2 ratio obtained before bevacizumab treatment. [From randomization until first documented Sp2/O2 ratio improvement, assessed up to 28 days.]
Time to improvement of Sp2/O2 ratio regarding the worst Sp2/O2 ratio obtained before bevacizumab treatment
Time to absence of oxygen need to maintain a saturation equal or over 93% [From randomization until patient doesn't need oxygen to mantain 93% saturation, assessed up to 28 days.]
Time to absence of oxygen need to maintain a saturation equal or over 93%
Favorable radiological evaluation. [From randomization until first documented radiology improvement, assessed up to 28 days.]
Dictated by 3 radiologists.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Respiratory distress: Tachypnea> 30 breaths / minute
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.