Clinical trial NCT04954014: Pilot Study of Single Dose Bevacizumab as Treatment for Acute Respiratory Distress Syndrome (ARDS) in COVID-19 Patients
Official title: Pilot Study of Single Dose Bevacizumab as Treatment for Acute Respiratory Distress Syndrome (ARDS) in COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: ARDS, Human
Coronavirus Infection
Keywords: ARDS
SARS-CoV-2
Bevacizumab
Lead sponsor: Maimónides Biomedical Research Institute of Córdoba
Sponsor class: OTHER
First posted: 2021-07-08
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mortality
timeFrame: After 28 days
Secondary outcomes:
measure: PaO2/FiO2
timeFrame: 6 hours before bevacizumab administration and 24 hours,72 hours,7 days,14 days and 28 days after.
measure: Clinical improvement according to scale recommended by WHO for COVID19
timeFrame: 24 hours, 72 hours, 7 days, 14 days and 28 days after treatment.
measure: Time to clinical improvement as stated in the National Early Warning Score 2 (NEWS)
timeFrame: From randomization until improvement of 2 points in the scale or until hospital discharge, whatever happens first, assessed up to 28 days.
measure: Time to improvement of oxygenation
timeFrame: From randomization until outcome event assessed up to 28 days.
measure: Time to improvement of Sp2/O2 ratio regarding the worst Sp2/O2 ratio obtained before bevacizumab treatment.
timeFrame: From randomization until first documented Sp2/O2 ratio improvement, assessed up to 28 days.
measure: Time to absence of oxygen need to maintain a saturation equal or over 93%
timeFrame: From randomization until patient doesn't need oxygen to mantain 93% saturation, assessed up to 28 days.
measure: Favorable radiological evaluation.
timeFrame: From randomization until first documented radiology improvement, assessed up to 28 days.
Other outcomes:
Locations:
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
state: Córdona
Study officials:
References: