Bevacizumab in Severe or Critically Severe Patients With COVID-19 Pneumonia-RCT (BEST-RCT)

• ClinicalTrials.gov Identifier: NCT04305106
• Recruitment Status: Recruiting
• First Posted: March 12, 2020
• Last Update Posted: March 26, 2020
• Sponsor: Qilu Hospital of Shandong University
• Collaborators: Renmin Hospital of Wuhan University; Ialy Moriggia Pelascini Gravedona Hospital S.p.A; Wuhan University; Jiangbei Union Hospital of Huazhong University of science and technology; Shandong Provincial Chest Hospital
• Information provided by (Responsible Party): Qilu Hospital of Shandong University

Study Description

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 the severe and critically severe patients. Pulmonary edema is the key detrimental feature of ALI/ARDS. Autopsy of patients died from COVID-19 reported that, pulmonary mucus exudation was severe, more 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. However, specific pharmacotherapy is lacking.Vascular endothelial growth factor (VEGF) is known as the most potent inducing factors to increase vascular permeability. Bevacizumab is an anti VEGF recombinant humanized monoclonal antibody, which has been used in anti-tumor treatment for 16 years. Evidence suggest that Bevacizumab is a promising drug for severe and critical COVID-19 patients.

Condition or disease	Intervention/treatment	Phase
COVID-19 Pneumonia	Drug: Bevacizumab	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Efficacy and Safety of Bevacizumab in Severe or Critical Patients With COVID-19--a Multicenter Randomized Controlled Clinical Trial
• Actual Study Start Date: March 17, 2020
• Estimated Primary Completion Date: June 30, 2020
• Estimated Study Completion Date: July 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bevacizumab Group	Drug: Bevacizumab; Bevacizumab 7.5mg/kg body weight + 0.9% NaCl 100ml, intravenous drip
No Intervention: Control Group

Outcome Measures

Primary Outcome Measures :

1. The time from randomization to clinical improvement [ Time Frame: No more than 28 days ]
   The time from randomization to an improvement of two points on a seven-category ordinal scale or live discharge from the hospital

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age: 18-80 years old, male and female;
2. Covid-19 confirmed cases;

3. Comply with any of the following:

   • Dyspnea, RR ≥ 30 times / min;

     • In resting state, transcutaneous oxygen saturation ≤ 93%;

       • Oxygenation index (PaO2 / FiO2) < 300MMHG;
4. Pulmonary imaging showed diffuse exudative lesions.

Exclusion Criteria:

1. Unable to obtain informed consent;
2. Patients with severe liver dysfunction (Child Pugh score ≥ C, or AST > 5 times of the upper limit), severe renal dysfunction (estimated glomerular filtration rate ≤ 30ml / min / 1.73 m2), or continuous renal replacement therapy, hemodialysis, peritoneal dialysis;
3. Patients with hypertension and unsatisfactory control of antihypertensive drugs (sitting systolic blood pressure > 160mmHg, or diastolic blood pressure > 100mmHg) had a history of hypertension crisis or hypertensive encephalopathy;
4. Patients with heart disease or clinical symptoms that can not be well controlled, such as NYHA class II or above of cardiac insufficiency, unstable angina, myocardial infarction within one year, supraventricular or ventricular arrhythmias need treatment or intervention;
5. Those with known hereditary bleeding tendency or coagulation dysfunction, those who had received full dose anticoagulant or thrombolytic therapy in the first 10 days of the group, or those who had taken nonsteroidal anti-inflammatory drugs with platelet inhibition in the first 10 days of the group (except those who had preventive use of low-dose aspirin ≤ 325mg / day);
6. In the first 6 months of the group, the patients who had thrombosis, such as ischemic stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism and other thrombotic diseases, and in the first 6 months of the group, the patients who had serious angiopathy (including aneurysms or arterial thrombosis requiring surgical treatment) were screened;
7. Patients with unhealed wounds, active gastric ulcer or fracture; patients with gastrointestinal perforation, gastrointestinal fistula, abdominal abscess and internal fistula in the first 6 months of the group; patients with major surgical history (including thoracotomy biopsy), major trauma (such as fracture) or possible surgery in the course of participating in the trial within 28 days before the group;
8. There were hemoptysis, gastrointestinal bleeding, central nervous system bleeding, nose bleeding and other serious and active bleeding patients within one month before admission;
9. There were malignant tumors in the past 5 years;
10. Those allergic to bevacizumab and its components;
11. Untreated active hepatitis patients and HIV positive patients;
12. Pregnant women, lactating women and planned pregnant women;
13. Have participated in other clinical trials or the researchers think it is not suitable to participate in this study.

Contacts and Locations

Contacts

Contact: Jiaojiao Pang, Dr; 18560089129; jiaojiaopang@126.com

Locations

China, Shandong

Qilu Hospital of Shandong University; Recruiting

Jinan, Shandong, China, 250012

Contact: Jiaojiao Pang, Dr +86 18560089129 jiaojiaopang@126.com

Sponsors and Collaborators

Qilu Hospital of Shandong University

Renmin Hospital of Wuhan University

Ialy Moriggia Pelascini Gravedona Hospital S.p.A

Wuhan University

Jiangbei Union Hospital of Huazhong University of science and technology

Shandong Provincial Chest Hospital

Investigators

• Principal Investigator: Yihai Cao, Dr; Qilu Hospital of Shandong University, Karolinska Institutet
• Principal Investigator: Yuguo Chen, Dr; Qilu Hospital of Shandong University

More Information

• Responsible Party: Qilu Hospital of Shandong University
• ClinicalTrials.gov Identifier: NCT04305106
• Other Study ID Numbers: QLEmer
• First Posted: March 12, 2020
• Last Update Posted: March 26, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors