Coronavirus InfectionsPhase 2BEST-CPNCT04275414
Bevacizumab in Severe or Critical Patients With COVID-19 Pneumonia
A Phase 2 study testing Bevacizumab Injection in people with Coronavirus Infections, run by Qilu Hospital of Shandong University at 3 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronavirus Infections
- What is being tested?
- Bevacizumab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 15 Feb 2020to 2 May 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
China2 sites
Qilu Hospital of Shandong University
Jinan, Shandong, 250012
Renmin Hospital of Wuhan University
Wuhan, Hubei
About this study
Official title: Effecacy and Safety of Bevacizumab in Severe Patients With Covid-19: a Pilot Study (BEST-CP)
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.
Read the 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.
- Conditions
- Coronavirus Infections
- Being tested
- Bevacizumab Injection
- Keywords
- COVID-19, Bevacizumab, pneumonia
- Medical subject headings
- Coronavirus Infections, COVID-19, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab InjectionDrug
Bevacizumab 500mg + normal saline (NS) 100ml, ivdrip ≥90min
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Bevacizumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio
Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio
Measured: 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
Measured: 7 days
Secondary outcomes (7)
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.
Measured: 28 days
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.
Measured: 7 days
Blood lymphocyte counts
Blood lymphocyte counts
Measured: 7 days
Level of CRP
Level of CRP
Measured: 7 days
Level of hs-CRP
Level of hs-CRP
Measured: 7 days
All-cause mortality
All-cause mortality
Measured: 28 days
Discharge rate
Discharge rate
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start15 Feb 2020
- Primary completion5 Apr 2020
- Study completion2 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronavirus InfectionsStudies of the same condition, open and under way.
- More trials run by Qilu Hospital of Shandong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Qilu Hospital of Shandong University
- Sponsor type
- University, hospital or other
- Collaborators
- Renmin Hospital of Wuhan University, Moriggia-Pelascini Gravedona Hospital
- Responsible party
- Sponsor
- Investigators
- Yuguo Chen, Dr, Principal investigator, Qilu Hospital of Shandong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04275414
- Sponsor's protocol ID
- QLEmer20200214
- Acronym
- BEST-CP
- Status last verified
- Feb 2020
- First submitted
- 14 Feb 2020
- Last updated
- 14 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 33547300
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effecacy and Safety of Bevacizumab in Severe Patients With Covid-19: a Pilot Study (BEST-CP)
- ClinicalTrials.gov ID
- NCT04275414
- Acronym / sponsor ID
- BEST-CP / QLEmer20200214
- Conditions
- Coronavirus Infections
- Keywords
- COVID-19, Bevacizumab, pneumonia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Qilu Hospital of Shandong UniversityUniversity, hospital or other
- Collaborators
- Renmin Hospital of Wuhan University, Moriggia-Pelascini Gravedona Hospital
- Study start
- 15 Feb 2020 (actual)
- Primary completion
- 5 Apr 2020 (actual)
- Study completion
- 2 May 2020 (actual)
- First posted
- 19 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bevacizumab plus standard care | Experimental | Drug: Bevacizumab InjectionUnder ECG monitoring, give bevacizumab 500mg + 0.9% sodium chloride solution 100ml via intravenous drip, time is no less than 90min. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab InjectionBevacizumab 500mg + normal saline (NS) 100ml, ivdrip ≥90min | Drug | bevacizumab plus standard care |
Primary outcome
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
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
7 secondary outcomes
Rate of improvement of oxygen-support status
Time frame: 28 days
The change of areas of pulmonary lesions shown on chest radiological imaging (chest CT or X-ray)
Time frame: 7 days
Blood lymphocyte counts
Time frame: 7 days
Level of CRP
Time frame: 7 days
Level of hs-CRP
Time frame: 7 days
All-cause mortality
Time frame: 28 days
Discharge rate
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2020.
- Derived from this study: PubMed 33547300Pang 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuguo Chen, Dr principal investigator
Qilu Hospital of Shandong University
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab Injection in people with Coronavirus Infections, run by Qilu Hospital of Shandong University at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04275414, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2020.