Protocol summary
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Study aim
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This study aims to investigate the effect of recombinant erythropoietin on the recovery process of COVID-19 patients.
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Design
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concealed, randomized, single blinded, phase 2 controlled clinical trial with two arm parallel group design of 20 patients, using the placebo in the control group.
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Settings and conduct
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This study will be performed at Shahid Mohammadi Hospital in Bandar Abbas. Patients enter the study after obtaining written consent, but will not know which group they belong to.
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Participants/Inclusion and exclusion criteria
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All positive COVID-19 patients who have Hb≤9 and at least one of the severe COVID-19 symptoms and are willing to cooperate in this project will be included in the study.
Patients with a history of coronary heart disease, thrombosis, deep vein thrombosis, chronic lung disease, diabetes mellitus, weakened immune system, end stage renal disease, liver disease, and patients with a history of taking oral contraceptive pills, systolic blood pressure more than 160 mm Hg, diastolic blood pressure more than 90 mm Hg and age over 65 and erythropoietin above 500 are excluded.
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Intervention groups
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Patients are divided into two groups. In group A, the standard treatment for COVID-19 patients with recombinant erythropoietin is prescribed. In group B, patients receive standard COVID-19 treatment with the placebo.
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Main outcome variables
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Patient clinical symptoms,
Laboratory examinations of patients and
Hemoglobin
General information
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Reason for update
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The expected recruitment end date was on 2020/12/21 but since we had a wide and careful exclusion criteria because of the adverse reactions of the medication, the recruitment (for both cases and controls) was not so easy and did not finish on the expected date and we are still recruiting now. Recruitment began on 2020/8/17 and the updated expected recruitment end date is 2021/8/1.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20200509047364N1
Registration date:
2020-08-09, 1399/05/19
Registration timing:
registered_while_recruiting
Last update:
2021-05-26, 1400/03/05
Update count:
2
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Registration date
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2020-08-09, 1399/05/19
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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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2020-06-21, 1399/04/01
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Expected recruitment end date
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2021-08-01, 1400/05/10
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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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Evaluation of the efficacy and safety of recombinant erythropoietin on the improvement of hospitalised COVID-19 patients
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Public title
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Effect of erythropoietin on COVID-19
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
All definitively positive COVID-19 patients with Hb≤9.
Having at least one of the severe symptoms of COVID-19, including tachypnea (breathing rate> 30 beats per minute), hypoxemia (O2 ≤93 saturation, the partial pressure ratio of arterial oxygen <300), Lung infiltration (> 50% of lung field within 24 to 48 hours), progressive lymphopenia, LDH>245 U/I, CRP>100
Exclusion criteria:
Patients with a history of coagulopathy
Patients with a history of thrombosis
Patients with a history of deep vein thrombosis
Patients with a history of chronic lung disease
Patients with a history of diabetes mellitus
Patients with weakened immune systems
Patients with a history of end stage renal disease
Patients with liver disease
Patients with a history of taking oral contraceptive pills (OCPs)
Patients with systolic blood pressure greater than 160 mmHg
Patients with diastolic blood pressure greater than 90 mmHg
Patients over 65 years of age
Patients with erythropoietin above 500
Patients with a history of myocardial infarction or unstable angina
Patients with a history of malignancy
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Age
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To 65 years old
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Gender
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Both
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Phase
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2
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Groups that have been masked
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Sample size
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Target sample size:
20
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Before assigning groups to individuals eligible to participate in the study, informed consent is completed for grouping individuals.
the person who has no role in admitting patients and assigning patients to random codes preparing random sequences using online tools (https://www.sealedenvelope.com/) and by permuted block randomization method.
Individualized random allocation is done in blocks with sizes 2 and 4, and with stratification based on gender.
eligibility criteria are monitored by the person responsible for admitting patients. Codes in a random sequence are assigned to patients by the treatment team without knowing that each code is in the intervention or placebo group. Patient codes are then matched to randomly generated sequence information for interventions.
(randomization concealment is done by the treatment team without informing the person responsible for admitting patients and the person who prepared the random sequence.)
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Blinding (investigator's opinion)
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Single blinded
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Blinding description
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In this study, all participants are aware of participating in this study and enter the study with their consent. All participants are unaware of which group of this study they are in and after grouping patients in the groups, Patients receive recombinant erythropoietin in the treatment group and receive a placebo in the control group.
The lead researcher, health care personnel, data collection officials, and those who evaluate the outcome are aware of the grouping of patients.
Those who prepare the draft of the article are unaware of the groupings if they do not cooperate in the above cases.
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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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Ethics committees
1
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Ethics committee
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Approval date
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2020-06-06, 1399/03/17
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Ethics committee reference number
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IR.HUMS.REC.1399.165
Health conditions studied
1
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Description of health condition studied
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Laboratory confirmed 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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Respiratory rate
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Timepoint
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At the beginning of the study (before the intervention) and day 5 after the intervention
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Method of measurement
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Pulse oximeter
2
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Description
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Oxygen saturation state and arterial oxygen partial pressure ratio
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Timepoint
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At the beginning of the study (before the intervention) and day 5 after the intervention
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Method of measurement
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Pulse oximeter
3
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Description
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Lung infiltration status
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Timepoint
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At the beginning of the study (before the intervention) and day 5 after the intervention
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Method of measurement
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chest x-ray
4
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Description
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LDH level's
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Timepoint
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At the beginning of the study (before the intervention) and day 5 after the intervention
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Method of measurement
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pathobiology laboratory
5
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Description
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CRP level's
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Timepoint
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At the beginning of the study (before the intervention) and day 5 after the intervention
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Method of measurement
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pathobiology laboratory
6
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Description
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Lymphocyte count
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Timepoint
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At the beginning of the study (before the intervention) and day 5 after the intervention
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Method of measurement
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pathobiology laboratory
7
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Description
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Endogenous erythropoietin level's
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Timepoint
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Beginning of study (before intervention)
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Method of measurement
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Pathobiology laboratory
8
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Description
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Patients' blood pressure
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Timepoint
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At the beginning of the study (before the intervention), during the intervention (5-day erythropoietin administration)
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Method of measurement
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Sphygmomanometer
Secondary outcomes
1
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Description
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Patients' blood hemoglobin levels
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Timepoint
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Start of study (before the intervention), day 5 after the intervention and 2 to 4 weeks after the intervention
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Method of measurement
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Pathobiology laboratory
Intervention groups
1
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Description
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Intervention group: Group A.: The standard drug treatment is based on the treatment protocols of the National Committee of COVID-19 and erythropoietin recombinant (EPREX Manufactured by Johnson and Johnson Pharmaceutical Company) 300 units / Kg or 4000IU as subcutaneous injection five times a day for 5 days and simultaneously Enoxaparin 1mg / kg SQ daily is also taken to prevent thrombosis. Patients' blood pressure, along with other vital signs, is checked regularly and at regular intervals. Standard drug treatment according to the treatment protocols of the National Committee for COVID-19 includes Hydroxychloroquine / Chloroquine Phosphate:• Hydroxychloroquine sulfate tablets 200 mg or chloroquine phosphate tablets 250 mg (equivalent to 150 mg base dose) 2 tablets every 12 hours on the first day and then one tablet every 12 hours for at least 7 days and up to 14 days. One of the following medications at the discretion and diagnosis of the treating physician:• Caltrate tablets (Lopinavir / Ritonavir) 50/200 mg every 12 hours 2 pieces after meals for at least 7 days and a maximum of 14 days• Tablets (Atazanavir / Ritonavir) 300/100 One tablet daily with food or Atazanavir 400 mg daily for at least 7 days and up to 14 days
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Category
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Treatment - Drugs
2
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Description
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Control group: Group B: The standard drug treatment is based on the treatment protocols of the National Committee for COVID-19 and the placebo(distilled water) is given as a subcutaneous injection five times a day for 5 days. Standard drug treatment according to the treatment protocols of the National Committee for COVID-19 includes Hydroxychloroquine / Chloroquine Phosphate:• Hydroxychloroquine sulfate tablets 200 mg or chloroquine phosphate tablets 250 mg (equivalent to 150 mg base dose) 2 tablets every 12 hours on the first day and then one tablet every 12 hours for at least 7 days and up to 14 days. One of the following medications at the discretion and diagnosis of the treating physician:• Caltrate tablets (Lopinavir / Ritonavir) 50/200 mg every 12 hours 2 pieces after meals for at least 7 days and a maximum of 14 days• Tablets (Atazanavir / Ritonavir) 300/100 One tablet daily with food or Atazanavir 400 mg daily for at least 7 days and up to 14 days
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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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Bandare-abbas 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