Bevacizumab in Patients With Severe Covid-19

NCT ID: NCT04305106

Last Updated: 2023-06-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

588 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-12

Study Completion Date

2023-12-31

Brief Summary

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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.

Detailed Description

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Evident increase of VEGF levels in serum has been displayed on novel pneumonia patients. The investigators also conducted a pilot study of 93 patients with severe COVID-19 that confirmed the significantly elevated level of plasma and serum VEGF.

At the beginning of 2020, the investigators proposed the concept of using anti-VEGF treatment for patients with severe COVID-19 and conducted a pilot study (NCT04275414). Among the 27 enrolled participants treated with bevacizumab, it was found that the clinical recovery status, PaO2/FiO2, and pulmonary exudation on imaging were significantly improved than the external controls in the same center during the same period. This provides good preliminary basis for this RCT.

Conditions

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COVID-19 Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Bevacizumab

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type 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.

Standard care

Intervention Type 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.

Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Standard care

Intervention Type 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.

Interventions

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Bevacizumab

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.

Intervention Type DRUG

Placebo

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.

Intervention Type OTHER

Standard care

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.

Intervention Type OTHER

Other Intervention Names

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Recombinant anti-VEGF humanized monoclonal antibody injection Inactive excipient

Eligibility Criteria

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Inclusion Criteria

1. Age: ≥18 years old, both genders;
2. Confirmed COVID-19 diagnosis (any body fluid tested positive for SARS-CoV-2 nucleic acid by PCR, or positive for SARS-CoV-2 antigen);
3. 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;
4. Article (3) above is newly appeared within 7 days;
5. Chest radiography or computed tomography shows bilateral chest infiltrates.

Exclusion Criteria

1. Unable to obtain informed consent.
2. Physician with more than 5 years of clinical experience determines that death was inevitable within 24 hours.
3. 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.
4. Uncontrolled hypertension (sitting systolic blood pressure\> 160mmHg, or diastolic blood pressure\>100mmHg); previous history of hypertension crisis or hypertensive encephalopathy.
5. 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.
6. Severe or above chronic obstructive pulmonary disease (GOLD grade, FEV1/FVC \< 0.5).
7. Hereditary bleeding tendency or coagulopathy;
8. 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.
9. 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.
10. Severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous system bleeding, and nosebleeds within 1 month before enrollment.
11. Malignant tumors within 5 years before enrollment.
12. Allergic to bevacizumab or its components.
13. Active tuberculosis, uncontrollable infection, untreated active hepatitis or HIV-positive patients.
14. Pregnant and lactating women and those planning to get pregnant.
15. Participated in other clinical trials, not considered suitable for this study by the researchers.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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China-Japan Friendship Hospital

OTHER

Sponsor Role collaborator

Renmin Hospital of Wuhan University

OTHER

Sponsor Role collaborator

Second Affiliated Hospital of Xi'an Jiaotong University

OTHER

Sponsor Role collaborator

Zhejing Provincial People's Hospital

UNKNOWN

Sponsor Role collaborator

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role collaborator

Anqing Municipal Hospital

OTHER

Sponsor Role collaborator

First Affiliated Hospital of Wannan Medical College

OTHER

Sponsor Role collaborator

The Fourth Affiliated Hospital Zhejing University School of Medicine

UNKNOWN

Sponsor Role collaborator

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role collaborator

Linyi People's Hospital

OTHER

Sponsor Role collaborator

Jining Medical University

OTHER

Sponsor Role collaborator

Jining First People's Hospital

OTHER

Sponsor Role collaborator

Weifang Second People's Hospital

UNKNOWN

Sponsor Role collaborator

Weifang Medical University

OTHER

Sponsor Role collaborator

Yantai Yuhuangding Hospital

OTHER

Sponsor Role collaborator

Weihai Municipal Hospital

OTHER

Sponsor Role collaborator

Rizhao People's Hospital

OTHER

Sponsor Role collaborator

Qingdao Municipal Hospital

OTHER

Sponsor Role collaborator

Qilu Hospital of Shandong University (Qingdao)

OTHER

Sponsor Role collaborator

Weifang People's Hospital

OTHER

Sponsor Role collaborator

Weifang Hospital of Traditional Chinese Medicine

UNKNOWN

Sponsor Role collaborator

Zibo Central Hospital

OTHER_GOV

Sponsor Role collaborator

Zibo Municipal Hospital

OTHER

Sponsor Role collaborator

Qilu Hospital of Shandong University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yihai Cao, Dr

Role: PRINCIPAL_INVESTIGATOR

Qilu Hospital of Shandong University, Karolinska Institutet

Yuguo Chen, Dr

Role: PRINCIPAL_INVESTIGATOR

Qilu Hospital of Shandong University

Locations

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Qilu Hospital of Shandong University

Jinan, Shandong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jiaojiao Pang, Dr

Role: CONTACT

18560089129

Facility Contacts

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Jiaojiao Pang, Dr

Role: primary

+86 18560089129

References

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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.

Reference Type BACKGROUND
PMID: 31986264 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33547300 (View on PubMed)

Other Identifiers

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QLEmer

Identifier Type: -

Identifier Source: org_study_id

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