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Bevacizumab in Severe or Critical Patients With COVID-19 Pneumonia (BEST-CP)

Primary Purpose

Coronavirus Infections

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Bevacizumab Injection

About this trial

This is an interventional treatment trial for Coronavirus Infections focused on measuring COVID-19, Bevacizumab, pneumonia

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18 to 80.
Confirmed COVID-19 diagnosis(including the clinically confirmed cases in Hubei).
Accord with any of the following: respiratory distress, RR ≥ 30 breaths/min; or SpO2 ≤ 93% at rest; or partial arterial oxygen pressure (PaO2) / fraction of inspiration O2 (FiO2) >100mmHg and ≤ 300mmHg (1mmHg = 0.133kPa).
Chest imaging confirms lung involvement and has inflammatory exudation or pleural effusion.

Exclusion Criteria:

Cannot obtain informed consent.
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.
Unsatisfactory controlled hypertension (seated 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.
Hereditary bleeding tendency or coagulopathy; received full-dose anticoagulant or thrombolytic therapy within10 days before enrollment, or have taken non-steroidal anti-inflammatory drugs with platelet suppression within 10 days before enrollment (Except those who use small doses of aspirin ≤325mg / day for preventive use).
Thrombosis within 6 months before enrollment. And from those patients, screen who had arterial / venous thromboembolic events, such as, ischemic stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, etc. within 1 year ahead of enrollment. 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.
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.

Sites / Locations

Renmin Hospital of Wuhan University
Qilu Hospital of Shandong University
Moriggia-Pelascini Gravedona Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

bevacizumab plus standard care

Arm Description

Under ECG monitoring, give bevacizumab 500mg + 0.9% sodium chloride solution 100ml via intravenous drip, time is no less than 90min.

Outcomes

Primary Outcome Measures

Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

Secondary Outcome Measures

Rate of improvement of oxygen-support status

The oxygen-support status includes 6 levels: mechanical ventilation, non-invasive ventilation, a transition status of alternate use of non-invasive ventilation and high-flow oxygen, high-flow oxygen, low-flow oxygen and ambient air. The improvement of oxygen-support status is defined as switch from a higher level of oxygen-support to a lower level.

The change of areas of pulmonary lesions shown on chest radiological imaging (chest CT or X-ray)

The areas of pulmonary lesions are analysised by a professional imaging software.

Blood lymphocyte counts

Level of CRP

Level of hs-CRP

All-cause mortality

Discharge rate

Full Information

NCT ID

NCT04275414

First Posted

February 14, 2020

Last Updated

September 10, 2020

Sponsor

Qilu Hospital of Shandong University

Collaborators

Renmin Hospital of Wuhan University, Moriggia-Pelascini Gravedona Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04275414

Brief Title

Bevacizumab in Severe or Critical Patients With COVID-19 Pneumonia

Acronym

BEST-CP

Official Title

Effecacy and Safety of Bevacizumab in Severe Patients With Covid-19: a Pilot Study (BEST-CP)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Completed

Study Start Date

February 15, 2020 (Actual)

Primary Completion Date

April 5, 2020 (Actual)

Study Completion Date

May 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Qilu Hospital of Shandong University

Collaborators

Renmin Hospital of Wuhan University, Moriggia-Pelascini Gravedona Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The novel identified coronavirus (SARS-CoV-2) in 2019 causes an nationwide outbreak as well as public health crisis in China, and expands globally. Pulmonary edema is one of the most detrimental symptoms and usually presents in severe and critical coronavirus disease (COVID-19), resulting in dyspnea, acute lung injury (ALI) ,acute respiratory distress syndrome (ARDS), and even death. Recent evidence revealed higher levels of blood Vascular Endothelial Growth Factor (VEGF) in COVID-19 patients compared with healthy controls. VEGF is considered as the most potent vascular permeability inducers. Numerous studies have revealed that VEGF was a key factor and a potential therapeutic target in ALI and ARDS. Bevacizumab, an anti-VEGF drug, approved by the FDA on February 26, 2004 and widely used in clinical oncotherapy, is a promising drug for ALI/ARDS in COVID-19 through suppression of pulmonary edema.

Detailed Description

In December 2019, a new identified coronavirus (SARS-CoV-2) outbreak in Wuhan, causes public health crisis in China and spreads worldwide. On February 11,2020, the World Health Organization officially named the disease caused by the new coronavirus "COVID-19". The Chinese Government takes stronger and harsher measures to control the progression of its outbreak. Meanwhile, five editions of "Diagnosis and Treatment for Novel Coronavirus-Infected Pneumonia" has been timely and continuously issued, which play extremely important roles in guiding the clinical management of COVID-19 nationwide in China. The symptoms of human infection with SARS-CoV-2 are generally fever, fatigue, dry cough and dyspnea. Noteworthy, a considerable percentage of COVID-19 cases have rapidly progressed to severe and critical type, among which acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the most common complications, resulting in a large number of pneumonia hospitalized patients requiring supplemental oxygen, mechanical ventilation, or even ECMO.Pulmonary edema is a detrimental feature as well as a key causal factor of ALI/ARDS. Vascular Endothelial Growth Factor (VEGF) is considered as the most potent vascular permeability inducers. Recent evidence has revealed higher VEGF levels in COVID-19 patients compared with healthy controls. The rise of VEGF levels may be caused by hypoxia, severe inflammation, and upregulation of the infected respiratory tract epithelium itself. Numerous studies have confirmed a key role of VEGF as potential therapeutic target in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due do increase vascular permeability and induce pulmonary edema. Thus, Bevacizumab, an anti-VEGF medication, may offer a unique approach to treat ALI/ARDS caused by COVID-19. Bevacizumab is a humanized monoclonal antibody with long half-life. It has been approved by the FDA on February 26, 2004 and widely used in clinical oncotherapy, with the pharmacokinetics and pharmacodynamics having been widely understood. Therefore, Bevacizumab is a promising drug for the treatment of ALI/ARDS as well as reduction of mortality in severe and critical COVID-19 patients through suppression of pulmonary edema.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronavirus Infections

Keywords

COVID-19, Bevacizumab, pneumonia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

bevacizumab plus standard care

Arm Type

Experimental

Arm Description

Under ECG monitoring, give bevacizumab 500mg + 0.9% sodium chloride solution 100ml via intravenous drip, time is no less than 90min.

Intervention Type

Drug

Intervention Name(s)

Bevacizumab Injection

Intervention Description

Bevacizumab 500mg + normal saline (NS) 100ml, ivdrip ≥90min

Primary Outcome Measure Information:

Title

Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

Description

Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

Time Frame

24 hours

Title

Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

Description

Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

Time Frame

7 days

Secondary Outcome Measure Information:

Title

Rate of improvement of oxygen-support status

Description

Time Frame

28 days

Title

The change of areas of pulmonary lesions shown on chest radiological imaging (chest CT or X-ray)

Description

The areas of pulmonary lesions are analysised by a professional imaging software.

Time Frame

7 days

Title

Blood lymphocyte counts

Description

Blood lymphocyte counts

Time Frame

7 days

Title

Level of CRP

Description

Level of CRP

Time Frame

7 days

Title

Level of hs-CRP

Description

Level of hs-CRP

Time Frame

7 days

Title

All-cause mortality

Description

All-cause mortality

Time Frame

28 days

Title

Discharge rate

Description

Discharge rate

Time Frame

28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18 to 80. Confirmed COVID-19 diagnosis(including the clinically confirmed cases in Hubei). Accord with any of the following: respiratory distress, RR ≥ 30 breaths/min; or SpO2 ≤ 93% at rest; or partial arterial oxygen pressure (PaO2) / fraction of inspiration O2 (FiO2) >100mmHg and ≤ 300mmHg (1mmHg = 0.133kPa). Chest imaging confirms lung involvement and has inflammatory exudation or pleural effusion. Exclusion Criteria: Cannot obtain informed consent. 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. Unsatisfactory controlled hypertension (seated 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. Hereditary bleeding tendency or coagulopathy; received full-dose anticoagulant or thrombolytic therapy within10 days before enrollment, or have taken non-steroidal anti-inflammatory drugs with platelet suppression within 10 days before enrollment (Except those who use small doses of aspirin ≤325mg / day for preventive use). Thrombosis within 6 months before enrollment. And from those patients, screen who had arterial / venous thromboembolic events, such as, ischemic stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, etc. within 1 year ahead of enrollment. 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yuguo Chen, Dr

Organizational Affiliation

Qilu Hospital of Shandong University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Renmin Hospital of Wuhan University

City

Wuhan

State/Province

Hubei

Country

China

Facility Name

Qilu Hospital of Shandong University

City

Jinan

State/Province

Shandong

ZIP/Postal Code

250012

Country

China

Facility Name

Moriggia-Pelascini Gravedona Hospital

City

Gravedona

Country

Italy

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

33547300

Citation

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.

Results Reference

derived

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Bevacizumab in Severe or Critical Patients With COVID-19 Pneumonia

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