Bevacizumab in Patients With Severe Covid-19

NCT04305106 | Unknown Phase 3 DMC

• 1 other identifier: QLEmer
• Study Type: interventional
• Target: 588
• Locations: 1 country
• Sites: 1

Brief Summary

The novel coronavirus (SARS-CoV-2) is a new strain of coronavirus found in human in 2019, which causes epidemic worldwide. Novel coronavirus disease (COVID-19) causes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in patients with severe COVID-19. Pulmonary edema is the key detrimental feature of ALI/ARDS. Autopsy of patients died from COVID-19 reported that, pulmonary mucus exudation was more severe and obvious than SARS infection. Pulmonary CT scanning and pathological findings also suggest that pulmonary edema caused by inflammatory exudation is a distinguished feature of COVID-19. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is known as the most potent factor to increase vascular permeability, with the induction effect 50,000 times stronger than histamine. Bevacizumab is an anti-VEGF recombinant humanized monoclonal antibody, which has been used in anti-tumor treatment since 2004, with considerable reliability and clinical safety. This trial will provide high level evidence to answer whether bevacizumab is efficacy and safe medication for patients with severe COVID-19.

Conditions

COVID-19 Pneumonia

Outcome Measures

Primary Outcomes (1)

• The time from randomization to clinical improvement

  The time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever comes first.

  28 days

Secondary Outcomes (11)

• Intubation rate

  From date of randomization until the date of discharge, up to 28 days

• Duration of mechanical ventilation (days)

  From date of randomization until the date of discharge, up to 28 days

• Duration of non-invasive ventilator or nasal high flow oxygen inhalation

  From date of randomization until the date of discharge, up to 28 days

• All-cause mortality

  From date of randomization until the date of discharge, up to 60 days

• Time to reach level 1 on the seven-category ordinal scale

  up to 60 days

Study Arms (2)

Bevacizumab

EXPERIMENTAL

Bevacizumab 7.5mg/kg body weight, intravenous drip, single-dose administration, and standard of care, including prophylactic doses of low molecular weight heparin or unfractionated heparin without contraindications, and therapeutic doses of anticoagulants with the evidence of thrombosis risk or occurrence.

Drug: Bevacizumab; Other: Standard care

Placebo

PLACEBO COMPARATOR

Placebo (inactive excipient) 7.5mg/kg body weight, intravenous drip, single-dose administration, and standard of care, including prophylactic doses of low molecular weight heparin or unfractionated heparin without contraindications, and therapeutic doses of anticoagulants with the evidence of thrombosis risk or occurrence.

Other: Placebo; Other: Standard care

Interventions

Bevacizumab DRUG

Bevacizumab (7.5mg/kg BW) + Saline (100ml) Bevacizumab will be administered in a single dose with no less than 90 minutes of intravenous infusion under ECG monitoring.

Also known as: Recombinant anti-VEGF humanized monoclonal antibody injection

Bevacizumab

Placebo OTHER

Placebo (7.5mg/kg BW) + Saline (100ml) The placebo drug will be administered in a single dose with no less than 90 minutes of intravenous infusion under ECG monitoring.

Also known as: Inactive excipient

Placebo

Standard care OTHER

Standard care, including prophylactic doses of low molecular weight heparin or unfractionated heparin without contraindications, and therapeutic doses of anticoagulants with the evidence of thrombosis risk or occurrence.

Bevacizumab; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥18 years old, both genders;
• Confirmed COVID-19 diagnosis (any body fluid tested positive for SARS-CoV-2 nucleic acid by PCR, or positive for SARS-CoV-2 antigen);
• Respiratory rate ≥ 30 times/min, partial pressure of oxygen (PaO2)/ fraction of inspiration O2 (FiO2)≤ 300mmHg (1mmHg = 0.133kPa), or SpO2 ≤ 93% at rest without supplemental oxygen;
• Article (3) above is newly appeared within 7 days;
• Chest radiography or computed tomography shows bilateral chest infiltrates.

You may not qualify if:

• Unable to obtain informed consent.
• Physician with more than 5 years of clinical experience determines that death was inevitable within 24 hours.
• Severe hepatic dysfunction (Child Pugh score ≥ C, or AST\> 5 times the upper limit); Severe renal dysfunction (estimated glomerular filtration rate ≤ 30mL/ min/1.73 m2) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
• Uncontrolled hypertension (sitting systolic blood pressure\> 160mmHg, or diastolic blood pressure\>100mmHg); previous history of hypertension crisis or hypertensive encephalopathy.
• Poorly controlled heart diseases, such as NYHA class II and above cardiac insufficiency, unstable angina pectoris, myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia need treatment or intervention.
• Severe or above chronic obstructive pulmonary disease (GOLD grade, FEV1/FVC \< 0.5).
• Hereditary bleeding tendency or coagulopathy;
• Arterial/venous thromboembolic events within 6 months before enrollment, such as ischemic stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, etc. Severe vascular disease (including aneurysms or arterial thrombosis requiring surgery) within 6 months before enrollment.
• Unhealed wounds, active gastric ulcers or fractures. Gastrointestinal perforation, gastrointestinal fistula, abdominal abscess, visceral fistula formation within 6 months before enrollment. Major surgery (including preoperative Chest biopsy) or major trauma (such as a fracture) within 28 days before enrollment. May have surgery during the trial.
• Severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous system bleeding, and nosebleeds within 1 month before enrollment.
• Malignant tumors within 5 years before enrollment.
• Allergic to bevacizumab or its components.
• Active tuberculosis, uncontrollable infection, untreated active hepatitis or HIV-positive patients.
• Pregnant and lactating women and those planning to get pregnant.
• Participated in other clinical trials, not considered suitable for this study by the researchers.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead
• China-Japan Friendship Hospital: collaborator
• Renmin Hospital of Wuhan University: collaborator
• Second Affiliated Hospital of Xi'an Jiaotong University: collaborator
• Zhejing Provincial People's Hospital: collaborator
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• Anqing Municipal Hospital: collaborator
• First Affiliated Hospital of Wannan Medical College: collaborator
• The Fourth Affiliated Hospital Zhejing University School of Medicine: collaborator
• Shandong Provincial Hospital: collaborator
• Linyi People's Hospital: collaborator
• Jining Medical University: collaborator
• Jining First People's Hospital: collaborator
• Weifang Second People's Hospital: collaborator
• Weifang Medical University: collaborator
• Yantai Yuhuangding Hospital: collaborator
• Weihai Municipal Hospital: collaborator
• Rizhao People's Hospital: collaborator
• Qingdao Municipal Hospital: collaborator
• Qilu Hospital of Shandong University (Qingdao): collaborator
• Weifang People's Hospital: collaborator
• Weifang Hospital of Traditional Chinese Medicine: collaborator
• Zibo Central Hospital: collaborator
• Zibo Municipal Hospital: collaborator

Study Sites (1)

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

RECRUITING

Related Publications (2)

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 BACKGROUND

• Pang J, Xu F, Aondio G, Li Y, Fumagalli A, Lu M, Valmadre G, Wei J, Bian Y, Canesi M, Damiani G, Zhang Y, Yu D, Chen J, Ji X, Sui W, Wang B, Wu S, Kovacs A, Revera M, Wang H, Jing X, Zhang Y, Chen Y, Cao Y. Efficacy and tolerability of bevacizumab in patients with severe Covid-19. Nat Commun. 2021 Feb 5;12(1):814. doi: 10.1038/s41467-021-21085-8.

  PMID: 33547300 BACKGROUND

MeSH Terms

Interventions

Bevacizumab; Standard of Care

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Yihai Cao, Dr

  Qilu Hospital of Shandong University, Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Yuguo Chen, Dr

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiaojiao Pang, Dr

CONTACT

18560089129; jiaojiaopang@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 12, 2020
• Study Start: January 12, 2023
• Primary Completion: November 30, 2023
• Study Completion: December 31, 2023
• Last Updated: June 27, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: On the day of article publication.
• Access Criteria: By inquiring of principal investigator or central contact person.

Locations

CN (1)