Protocol summary
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Study aim
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Determining the effect of bosentan on clinical outcomes of hospitalized patients with COVID-19 infection in comparison with routine protocol
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Design
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Double-blind randomized controlled clinical trial
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Settings and conduct
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In this study, COVID-19 patients, hospitalized in Shahid Mostafa Khomeini and Imam Khomeini hospitals with the mentioned inclusion and exclusion criteria will be studied. Bosentan and placebo tablets are similar, and patients and researchers are unaware of labeling. Bosentan 62.5 mg tablets will be given twice daily. Patients are followed up daily. After discharge, they will be followed up for 30 days from the time of intervention.
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Participants/Inclusion and exclusion criteria
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Inclusion Criteria:
• Written informed consent; Age over 18 years; Laboratory-confirmed SARS-CoV-2 infection;
Exclusion Criteria:
• Pregnancy; Lactation; Glibenclamide Consumption; Cyclosporine Consumption; Aminotransferases > 3 times normal; Allergy to bosentan
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Intervention groups
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Oral Bosentan 62.5 mg, twice daily, for 30 days.
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Main outcome variables
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The time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a WHO 11 point clinical progression scale or live discharge from the hospital, whichever came first.
General information
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Reason for update
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Start recruitment process
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20211203053263N2
Registration date:
2022-02-26, 1400/12/07
Registration timing:
prospective
Last update:
2022-07-19, 1401/04/28
Update count:
2
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Registration date
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2022-02-26, 1400/12/07
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2022-02-27, 1400/12/08
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Expected recruitment end date
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2022-05-29, 1401/03/08
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Comparison of the effect of bosentan with routine protocol on clinical outcomes of hospitalized patients with COVID-19 infection.
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Public title
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Bosentan in hospitalized patients with COVID-19 infection
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Written informed consent prior to initiation of study.
Age over 18 years.
Laboratory-confirmed SARS-CoV-2 infection determined by PCR less than 72 hours before randomization.
Illness of any duration, and at least one of the following:Radiographic infiltrates by imaging , OR Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air, OR Requiring mechanical ventilation and/or supplemental oxygen.
Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study.
Exclusion criteria:
Pregnancy or Lactation
Glibenclamide Consumption
Cyclosporine Consumption
Aminotransferases > 3 times normal
Allergy to bosentan
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Age
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From 18 years old
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Gender
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Both
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Phase
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3
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Groups that have been masked
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- Participant
- Care provider
- Investigator
- Outcome assessor
- Data analyser
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Sample size
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Target sample size:
200
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Permuted Block Randomization will be used for random allocation. The size of the blocks will randomly selected. There are 4, random blocks, each has an equal number of interventions and controls. In the 4 blocks, two allocations are considered for the intervention group and two allocations for the control group. Random Allocation Software will be used for this purpose. The concealment will be done using sequentially numbered, sealed envelopes.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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Blinding in this study is double blind that the drug and placebo are labeled as "Group A" and "Group B". They are quite similar in appearance and the person participating in the study and the person distributing the medicine does not know about this labeling.
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Placebo
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Used
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Assignment
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Parallel
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Other design features
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This study is an adaptive and add on trial.
Ethics committees
1
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Ethics committee
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Approval date
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2022-02-21, 1400/12/02
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Ethics committee reference number
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IR.MEDILAM.REC.1400.220
Health conditions studied
1
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Description of health condition studied
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COVID-19
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ICD-10 code
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U07.1
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ICD-10 code description
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COVID-19, virus identified
Primary outcomes
1
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Description
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The time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a WHO 11 point clinical progression scale or live discharge from the hospital, whichever came first.
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Timepoint
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During hospitalization
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Method of measurement
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WHO 11 point clinical progresson scale
Secondary outcomes
1
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Description
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Proportion of patients in each category of the WHO 11 point clinical progression scale on day 30 after randomization
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Timepoint
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Day 30
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Method of measurement
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WHO 11 point clinical progression scale
2
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Description
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Duration of mechanical ventilation
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Timepoint
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During hospitalization
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Method of measurement
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Mechanical ventilation, Observation
3
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Description
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Duration of hospitalization in survivors
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Timepoint
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During intervention
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Method of measurement
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Observation, Medical report
4
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Description
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The composite of symptomatic deep venous thrombosis; pulmonary embolism; arterial thromboembolism; myocardial infarction; ischemic stroke, up to 30 days after treatment initiation
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Timepoint
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30 days from intervention
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Method of measurement
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Observation
5
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Description
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30 days mortality
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Timepoint
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30 days from intervention
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Method of measurement
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Observation, Medical report
6
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Description
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Sarcopenia
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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EWGSOP2 criteria
7
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Description
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Functional status
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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Post-Covid Functional Scale
8
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Description
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dyspnea
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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MMRC dyspnea scale
9
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Description
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fatigability
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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chalder fatigue scale
10
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Description
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Sleep disorders
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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Pittsburgh Sleep Questionnaire
11
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Description
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Brain fog
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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Visual Analog Scale
12
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Description
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Loss of taste and smell
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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Visual Analog Scale
13
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Description
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thromboembolic events
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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clinical and paraclinical exam
14
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Description
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Changes in serum level of CMP
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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Serum measurement
15
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Description
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Change in Weight
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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Weight scale
16
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Description
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Changes in Subject's quality of life
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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Health Survey Questionnaire
17
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Description
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Assessment of sexual function
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Timepoint
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Change from baseline at 3-12 months
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Method of measurement
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questionnaire
Intervention groups
1
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Description
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Intervention group: The study group in addition to the drugs used in the treatment of COVID-19 (approved by the National Committee), is treated with oral Bosentan 62.5 mg twice a day for 30 days. Patients will be followed for 30 days for recovery or discharge, duration of mechanical ventilation dependency, length of hospital stay, mortality, and thromboembolic events.
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Category
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Treatment - Drugs
2
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Description
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Control group: The control group, in addition to the drugs used in the treatment of COVID-19 (approved by the National Committee), receive a placebo twice a day for 30 days. Patients will be followed for 30 days for recovery or discharge, duration of mechanical ventilation dependency, length of hospital stay, mortality, and thromboembolic events.
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Category
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Placebo
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Ilam University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available