NCT04275414

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
27

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2020

Shorter than P25 for phase_2

Geographic Reach
2 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 14, 2020

Completed
1 day until next milestone

Study Start

First participant enrolled

February 15, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 19, 2020

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 5, 2020

Completed
27 days until next milestone

Study Completion

Last participant's last visit for all outcomes

May 2, 2020

Completed
Last Updated

September 14, 2020

Status Verified

February 1, 2020

Enrollment Period

2 months

First QC Date

February 14, 2020

Last Update Submit

September 10, 2020

Conditions

Coronavirus Infections

Keywords

COVID-19Bevacizumabpneumonia

Outcome Measures

Primary Outcomes (2)

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

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

    24 hours

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

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

    7 days

Secondary Outcomes (7)

  • Rate of improvement of oxygen-support status

    28 days

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

    7 days

  • Blood lymphocyte counts

    7 days

  • Level of CRP

    7 days

  • Level of hs-CRP

    7 days

  • +2 more secondary outcomes

Study Arms (1)

bevacizumab plus standard care

EXPERIMENTAL

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

Drug: Bevacizumab Injection

Interventions

Bevacizumab InjectionDRUG

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

bevacizumab plus standard care

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Renmin Hospital of Wuhan University

Wuhan, Hubei, China

Location

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

Location

Moriggia-Pelascini Gravedona Hospital

Gravedona, Italy

Location

Related Publications (1)

  • 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: 33547300DERIVED

MeSH Terms

Conditions

Coronavirus InfectionsCOVID-19Pneumonia

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Coronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsVirus DiseasesInfectionsPneumonia, ViralRespiratory Tract InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Yuguo Chen, Dr

    Qilu Hospital of Shandong University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 14, 2020

First Posted

February 19, 2020

Study Start

February 15, 2020

Primary Completion

April 5, 2020

Study Completion

May 2, 2020

Last Updated

September 14, 2020

Record last verified: 2020-02

Locations

CN(2)IT(1)