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

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ClinicalTrials.gov Identifier: NCT04275414
Recruitment Status : Recruiting
First Posted : February 19, 2020
Last Update Posted : April 3, 2020
Sponsor:
Collaborators:
Renmin Hospital of Wuhan University
Moriggia-Pelascini Gravedona Hospital
Information provided by (Responsible Party):
Qilu Hospital of Shandong University

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.

Condition or disease Intervention/treatment Phase
Coronavirus Infections Drug: Bevacizumab Injection Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Bevacizumab in the Treatment of Severe or Critical Patients With COVID-19 Pneumonia (BEST-CP)
Actual Study Start Date : February 15, 2020
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : May 2020


Arm Intervention/treatment
Experimental: bevacizumab plus regular therapy
Under ECG monitoring, give bevacizumab 500mg + 0.9% sodium chloride solution 100ml via intravenous drip, time is no less than 90min. Other treatment follows the recommendations issued by Chinese government.
Drug: Bevacizumab Injection
Bevacizumab 500mg + normal saline (NS) 100ml, ivdrip ≥90min
Other Name: An ke da




Primary Outcome Measures :
  1. Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio [ Time Frame: 24 hours ]
    Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

  2. Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio [ Time Frame: 72 hours ]
    Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

  3. Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio [ Time Frame: 7 days ]
    Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio


Secondary Outcome Measures :
  1. Degree of dyspnea (Liker scale) [ Time Frame: 72 hours ]
    Liker scale: The patient grades his current breathing compared to when he first started the drug (from -3 to 3). "0" = no change, "1" =minimally better, "2" =moderately better, "3" =markedly better, "-1" =minimally worse, "-2" =moderately worse, "-3" =markedly worse

  2. Degree of dyspnea (Liker scale) [ Time Frame: 7 days ]
    The patient grades the current breathing condition of himself compared to when he first started the drug (from -3 to 3).

  3. Degree of dyspnea (VAS) [ Time Frame: 72 hours ]
    Visual analog scale (VAS): The patient draws a horizontal line on an axial graph (from 0 to 100) to show the degree of how he feels about breathing. The number "0" equals the worst breathing the patient has ever felt and the number "100" equals the best he has ever felt.

  4. Degree of dyspnea (VAS) [ Time Frame: 7 days ]
    Visual analog scale (VAS): The patient draws a horizontal line on an axial graph (from 0 to 100) to show the degree of how he feels about breathing. The number "0" equals the worst breathing the patient has ever felt and the number "100" equals the best he has ever felt.

  5. The area of lung lesions on Chest CT [ Time Frame: 7 days ]
    The degree of exudation on Chest CT

  6. The degree of lung exudation on Chest CT [ Time Frame: 7 days ]
    The degree of lung exudation on Chest CT

  7. SpO2 [ Time Frame: 24 hours ]
    transcutaneous oxygen saturation

  8. SpO2 [ Time Frame: 72 hours ]
    transcutaneous oxygen saturation

  9. SpO2 [ Time Frame: 7 days ]
    transcutaneous oxygen saturation

  10. PaO2 [ Time Frame: 24 hours ]
    Partial arterial oxygen pressure

  11. PaO2 [ Time Frame: 72 hours ]
    Partial arterial oxygen pressure

  12. PaO2 [ Time Frame: 7 days ]
    Partial arterial oxygen pressure

  13. CRP [ Time Frame: 72 hours ]
    CRP

  14. CRP [ Time Frame: 7 days ]
    CRP

  15. hs-CRP [ Time Frame: 72 hours ]
    hs-CRP

  16. hs-CRP [ Time Frame: 7 days ]
    hs-CRP

  17. All-cause mortality [ Time Frame: 7 days ]
    All-cause mortality

  18. All-cause mortality [ Time Frame: 14 days ]
    All-cause mortality



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 to 80.
  2. Confirmed COVID-19 diagnosis(including the clinically confirmed cases in Hubei).
  3. Accord with any of the following: ① Respiratory distress, RR ≥ 30 breaths/min; ② SpO2 ≤ 93% at rest; ③ Partial arterial oxygen pressure (PaO2) / Fraction of inspiration O2 (FiO2) ≤ 300mmHg (1mmHg = 0.133kPa).
  4. Chest imaging confirms lung involvement and has inflammatory exudation or pleural effusion.

Exclusion Criteria:

  1. Cannot obtain informed consent.
  2. 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.
  3. Unsatisfactory controlled hypertension (seated systolic blood pressure> 160mmHg, or diastolic blood pressure> 100mmHg); previous history of hypertension crisis or hypertensive encephalopathy.
  4. 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.
  5. 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).
  6. 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.
  7. 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.
  8. Severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous system bleeding, and nosebleeds within 1 month before enrollment.
  9. Malignant tumors within 5 years before enrollment.
  10. Allergic to bevacizumab or its components.
  11. Untreated active hepatitis or HIV-positive patients.
  12. Pregnant and lactating women and those planning to get pregnant.
  13. Participated in other clinical trials, not considered suitable for this study by the researchers.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04275414


Contacts
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Contact: Jiaojiao Pang, Dr (086)0531-82166843 jiaojiaopang@126.com

Locations
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China, Hubei
Renmin Hospital of Wuhan University Recruiting
Wuhan, Hubei, China
Contact: Jie Wei         
China, Shandong
Qilu Hospital of Shandong University Recruiting
Jinan, Shandong, China, 250012
Contact: Jiaojiao Pang    (086)0531-82166843    jiaojiaopang@126.com   
Italy
Moriggia-Pelascini Gravedona Hospital Recruiting
Gravedona, Italy
Contact: Gianmarco Aondio         
Sponsors and Collaborators
Qilu Hospital of Shandong University
Renmin Hospital of Wuhan University
Moriggia-Pelascini Gravedona Hospital
Investigators
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Principal Investigator: Yuguo Chen, Dr Qilu Hospital of Shandong University
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Responsible Party: Qilu Hospital of Shandong University
ClinicalTrials.gov Identifier: NCT04275414    
Other Study ID Numbers: QLEmer20200214
First Posted: February 19, 2020    Key Record Dates
Last Update Posted: April 3, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Qilu Hospital of Shandong University:
COVID-19
Bevacizumab
pneumonia
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors