AzTrials
AzTrials

Corona Virus InfectionPhase 3BEVANCT04822818

EFFICACY and SAFETY OF BEVACIZUMAB (ZIRABEV®) IN PATIENTS WITH SEVERE HYPOXEMIC COVID-19

A Phase 3 study testing BEVA+SOC and SOC in people with Corona Virus Infection and SARS (Severe Acute Respiratory Syndrome), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the most frequent complications of the COVID-19 pandemic. In these conditions, hypoxemia may result from : i) a pulmonary vascular dilatation resulting from an impaired hypoxic pulmonary vasoconstriction and leading to ventilation-perfusion… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BEVA+SOC and SOC
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
1 siteFrance
Study dates
17 Apr 2021to 11 Jul 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients included in the CORIMUNO-19 cohort
  • Patients hospitalized in conventional ward or in the ICU belonging to the following groups: OMS Progression scale 6, 7, 8 AND no acute pulmonary embolism on CT-scan performed in the preceding 72 hours no pulmonary evident bacterial coinfection or superinfection evaluated by non-invasive procedures (serology, antigens, nasopharynx PCR, sputum examination, blood cultures…)

Who cannot join

  • Patients in OMS progression class 9
  • Patients with exclusion criteria to the CORIMUNO-19 cohort
  • Pregnancy
  • Active cancer with ongoing treatment
  • acute use of NIV for COPD exacerbation or cardiac decompensation associated to COVID-19
  • Oxygen patient requiring long-term oxygen before hospitalization
Show all 16Show fewer
  • Patient already included in an interventional research
  • Risk of bleeding especially hemoptysis, active venous or arterial thromboembolic disease and recent surgery during the last 3 weeks
  • Hypersensitivity to the active substance (bevacizumab) or to any of the excipients (sucrose, succinic acid, disodium edetate, polysorbate 80, sodium hydroxide, water for injection
  • Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies
  • Persistant uncontrolled arterial hypertension after using to anti-hypertensive drugs
  • Current documented bacterial infection not controlled by antibiotics.
  • Active viral diseases (especially active herpes, chickenpox, shingles),
  • Active tuberculosis or disseminated strongyloidiasis
  • patient with known active hepatitis or with increased level of SGOT or SGPT ≥5N
  • Patient with anormal laboratory results: Absolute neutrophil count (ANC) ≤ 1.0 x 109/L, Platelets (PLT) < 50 G /L

Trial locations and contacts

1 site in 1 country.

France1 site

  • Hôpital TENON

    Paris

Other trials in France

About this study

Official title: TRIAL EVALUATING EFFICACY and SAFETY OF BEVACIZUMAB (ZIRABEV®) IN PATIENTS WITH SEVERE HYPOXEMIC COVID-19, NESTED IN THE CORIMUNO-19 COHORT

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the most frequent complications of the COVID-19 pandemic. In these conditions, hypoxemia may result from : i) a pulmonary vascular dilatation resulting from an impaired hypoxic pulmonary vasoconstriction and leading to ventilation-perfusion mismatching within the lungs and ii) thrombosis-mediated perfusion defects. Pulmonary vascular dilation might be due to a relative failure of the physiological acute hypoxic pulmonary vasoconstriction, in the context of an over-activation of a regional vasodilatation cascade, as part of a dysfunctional inflammatory process. Perfusion abnormalities associated with pulmonary vascular dilation are suggestive of intrapulmonary shunting toward areas where gas exchange is impaired, ultimately leading to a worsening ventilation-perfusion mismatch, a regional hypoxia and a profound hypoxemia.

Increased plasma levels of VEGF have been reported in moderate to severe COVID-19 pneumonia, highlighting the role of VEGF in the pathophysiology of the disease. A better prognosis has been reported in critically ill patients with lower levels of growth factors, HGF and VEGF-A at the time of ICU admission. Recent data of the study NCT 04275414 by Pang J et al have suggested that patients receiving a single-dose of bevacizumab have improved their oxygen support status in 92% of cases during a 28-day follow-up period, as compared with 62% of cases in an external cohort receiving standard care.

Correcting endothelial permeability and vasodilatation with VEGF-targeted therapy could allow repair damaged vascular endothelium, have an indirect anti-inflammatory effect (limiting alveolar exudation of circulating inflammatory and procoagulant mediators) and improve oxygenation and therefore reduce the proportion of patients with severe forms requiring ICU referral and finally patient death. This clinical trial will therefore focus on the specific efficacy of bevacizumab in COVID-19 patients with severe hypoxemia.

Being tested
BEVA+SOC, SOC
Keywords
COVID-19 pneumonia, severe hypoxemia, VEGF, bevacizumab
Medical subject headings
Coronavirus Infections, Severe Acute Respiratory Syndrome, Virus Diseases, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Respiratory Tract Infections, Respiratory Tract Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BEVA+SOCDrug

    Bevacizumab : 7.5 mg / kg (with a maximum of 750 mg) on day 1 (D1) SOC : patients will receive the best of standard of care including corticosteroids, anticoagulant, antibiotics and tociluzimab

  • SOCDrug

    patients will receive the best of standard of care including corticosteroids, anticoagulant, antibiotics and tociluzimab

Study groups in NCT04822818
Study groupRoleWhat they receive
Bevacizumab + SOCExperimentalBevacizumab : 7.5 mg / kg (with a maximum of 750 mg) on day 1 (D1) SOC : patients will receive the best of standard of care including corticosteroids, anticoagulant, antibiotics and tociluzimab
Receives: Drug: BEVA+SOC
SOCActive comparatorSOC : patients will receive the best of standard of care including corticosteroids, anticoagulant, antibiotics and tociluzimab
Receives: Drug: SOC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The time to recovery for a category 0 to 5 on the WHO Progression scale

    Defined as the first day on which the patient meets the criteria for category 0 to 5 on the OMS Progression scale

    Measured: 28 days after randomization

Secondary outcomes (8)

  1. Clinical status on the OMS Progression scale

    WHO progression scale:

    Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10

    Measured: at 7, 14, and 28 days after randomization

  2. Overall survival

    Time to death after randomization

    Measured: at 7, 14, and 28 days after randomization

  3. Ventilator free days

    Measured: at 7, 14, and 28 days after randomization

  4. High flow free days

    Measured: at 7, 14, and 28 days after randomization

  5. Time to oxygen supply weaning

    Measured: at 7, 14, and 28 days after randomization

  6. Changes in VEGF plasma levels

    Measured: at 7, and 14 days after randomization

  7. Comparison of the incidence of Grade 3 or 4 events will be will be described in each group with their 95% CI

    Description : defined according to CTCAE v5.0 will be will be described in each group with their 95% CI

    Measured: Day 28

  8. Proportion of Adverse Event

    will be described in each group with their 95% CI

    Measured: Day 28, day 120 after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Mar 2021
  2. Study start17 Apr 2021
  3. Primary completion10 Apr 2022
  4. Study completion11 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04822818
Sponsor's protocol ID
APHP200375-BEVA
Acronym
BEVA
Status last verified
Dec 2022
First submitted
25 Mar 2021
Last updated
28 Dec 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BEVA+SOC and SOC in people with Corona Virus Infection and SARS (Severe Acute Respiratory Syndrome), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The time to recovery for a category 0 to 5 on the WHO Progression scale (time frame: 28 days after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04822818.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in