Pilot Study for Cyproheptadine in Hospitalized Patient for COVID-19
Primary Purpose
Viral Pneumonia, COVID-19 Pneumonia, Serotonin Syndrome
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Cyproheptadine Hydrochloride 4 MG
Sponsored by
About this trial
This is an interventional treatment trial for Viral Pneumonia
Eligibility Criteria
Inclusion Criteria:
- Women and men aged 18 and over.
- Requiring treatment for COVID 19 and whose clinical status corresponds to a score equal to or greater than 5 on the WHO Clinical Progression Scale.
- For the prospective study, able to give informed consent.
- Not presenting an exclusion criterion
Exclusion Criteria:
- Pregnancy
- Patients with pre-existing terminal condition with life expectancy < 6 months
- Patient with clinically frailty according to a score of the clinical frailty scale equal or superior to 7
- Patients with pre-existing severe lung disease requiring home oxygen therapy.
- Patients with pre-existing severe hepatic cirrhosis (Grade C according to the Child-Pugh classification)
- Patients with pre-existing kidney failure (GFR strictly less than 15ml/min/1.73m2 according The KDIGO classification) or requiring renal replacement therapy.
- Patients with pre-existing angle-closure glaucoma
- Patient with symptomatic prostatic hypertrophy or bladder neck obstruction
- Patient with history of seizure disorder
- Patient with history of adverse reaction to antihistamines or to Cyproheptadine
- Patients taking routinely SSRI or monoamine oxidase inhibitor therapy.
- Patients presenting severe hepatic cytolysis with ALP >5 ULN at the time of study inclusion.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cyproheptadine
Arm Description
Outcomes
Primary Outcome Measures
Clinical evolution according the WHO Clinical Progression Scale
World Health Organisation Clinical Progression Scale for COVID 19 Minimal value 0 (uninfected) to maximal value 10 (Dead)
Secondary Outcome Measures
Incidence of Treatment-Emergent Adverse Events
Safety evaluation, as measured by suspected as related to cyproheptadine during the first 28 days after inclusion in the study:
Adverse events
Adverse drug reactions
Serious adverse event and adverse drug reaction
Recruitement rate
Completion rate
Rate of Death from any cause
Total number of days of hospitalisation
Total number of days of hospitalization in the ICU
Total number of days of mechanical ventilation
Daily ROX ratio
Worst value of ROX ratio (SPO2/FiO2/Respiratory Rate) at D3,5,7,10,14,28
Creatinine level
Worst value of Laboratory assessment of Creatinine at Days 3,5,7,10,14,28 after inclusion in the study
Alanine amino transferase level
Worst value of Laboratory assessment of Alanine amino transferase at Days 3,5,7,10,14,28 after inclusion in the study
C Reactive Protein level
Worst value of Laboratory assessment of CRP at Days 3,5,7,10,14,28 after inclusion in the study
D-Dimere level
Worst value of Laboratory assessment of D-Dimere at Days 3,5,7,10,14,28 after inclusion in the study
Platelet count
Worst value of Laboratory assessment of platelet count at Days 3,5,7,10,14,28 after inclusion in the study
Full Information
NCT ID
NCT04876573
First Posted
May 3, 2021
Last Updated
May 5, 2021
Sponsor
Ciusss de L'Est de l'Île de Montréal
1. Study Identification
Unique Protocol Identification Number
NCT04876573
Brief Title
Pilot Study for Cyproheptadine in Hospitalized Patient for COVID-19
Official Title
Pilot Study for Cyproheptadine in Hospitalized Patient for COVID-19: a Single-center, Observational Retrospective-prospective Comparative Study.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
June 1, 2021 (Anticipated)
Primary Completion Date
December 31, 2021 (Anticipated)
Study Completion Date
January 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ciusss de L'Est de l'Île de Montréal
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Pilot study for evaluating the feasibility, security and efficacy of the use of Cypropheptadine, an antihistaminic and antiserotonin drug, as an adjunct of the standardized treatment in a population of patient who are hospitalized and requiring oxygen therapy for COVID-19.
Detailed Description
Background :
Biochemical studies have revealed a significant increase in plasma serotonin levels in patients suffering from COVID-19 multi-organ disease, which appears to be a consequence of platelet hyperreactivity and dysfunction.
Among the several potential therapeutic pathways available to modulate this serotonin dysregulation is the use of cyproheptadine, an Anti-serotonergic antihistamine that can potentially improve organ dysfunction related to elevated plasma serotonin levels.
The investigators hypothesize that treatment with cyproheptadine will improve clinical course in these patients.
Objectives:
Primary objective
Compare the clinical course according to the WHO ordinal severity score for COVID-19, between a retrospective and a prospective interventional cohort of patient hospitalized in the same hospital.
Secondary objectives
Evaluate the safety of the use of the cyproheptadine hospitalized patients presenting COVID 19.
Evaluate the study in term of Feasibility Recruitment rate and Study completion rate.
Evaluate the outcome in term of Death, Needs of Non-invasive and/or invasive mechanical ventilation and Total Length of hospitalization Evaluate the evolution of clinical indicators of oxygenation and blood parameters of inflammation, renal function, hepatic cytolysis and platelet count.
Design:
This pilot trial is a non-blinded clinical designed to access the feasibility, the security and the efficacy of the use of Cyproheptadine in patient hospitalized in a single center for Covid-19 with comparison between:
A retrospective cohort study of patient and treated by standard care according to WHO international guidelines.
A prospective study of a cohort of patients hospitalized for covid 19 taking oral Cyproheptadine during 10 days in addition to standard care according to WHO international guidelines. The prospective study will be divided into two different phases in which two different doses of cyproheptadine will be administered.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Viral Pneumonia, COVID-19 Pneumonia, Serotonin Syndrome, Platelet Dysfunction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cyproheptadine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cyproheptadine Hydrochloride 4 MG
Intervention Description
Phase 1: Cyproheptadine 4 mg three time a day for 10 days, per oral administration associated to Standard care of COVID 19 patient currently recommend by WHO
Phase 2: Cyproheptadine 8 mg three time a day for 10 days, per oral administration associated to Standard care of COVID 19 patient currently recommend by WHO
The dose will be adjusted according to the renal function.
Primary Outcome Measure Information:
Title
Clinical evolution according the WHO Clinical Progression Scale
Description
World Health Organisation Clinical Progression Scale for COVID 19 Minimal value 0 (uninfected) to maximal value 10 (Dead)
Time Frame
Approximately 28 days
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
Safety evaluation, as measured by suspected as related to cyproheptadine during the first 28 days after inclusion in the study:
Adverse events
Adverse drug reactions
Serious adverse event and adverse drug reaction
Time Frame
Approximately 28 days
Title
Recruitement rate
Time Frame
6 month
Title
Completion rate
Time Frame
6 month
Title
Rate of Death from any cause
Time Frame
Approximately 28 days
Title
Total number of days of hospitalisation
Time Frame
Approximately 28 days
Title
Total number of days of hospitalization in the ICU
Time Frame
Approximately 28 days
Title
Total number of days of mechanical ventilation
Time Frame
Approximately 28 days
Title
Daily ROX ratio
Description
Worst value of ROX ratio (SPO2/FiO2/Respiratory Rate) at D3,5,7,10,14,28
Time Frame
Approximately 28 days
Title
Creatinine level
Description
Worst value of Laboratory assessment of Creatinine at Days 3,5,7,10,14,28 after inclusion in the study
Time Frame
Approximately 28 days
Title
Alanine amino transferase level
Description
Worst value of Laboratory assessment of Alanine amino transferase at Days 3,5,7,10,14,28 after inclusion in the study
Time Frame
Approximately 28 days
Title
C Reactive Protein level
Description
Worst value of Laboratory assessment of CRP at Days 3,5,7,10,14,28 after inclusion in the study
Time Frame
Approximately 28 days
Title
D-Dimere level
Description
Worst value of Laboratory assessment of D-Dimere at Days 3,5,7,10,14,28 after inclusion in the study
Time Frame
Approximately 28 days
Title
Platelet count
Description
Worst value of Laboratory assessment of platelet count at Days 3,5,7,10,14,28 after inclusion in the study
Time Frame
Approximately 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women and men aged 18 and over.
Requiring treatment for COVID 19 and whose clinical status corresponds to a score equal to or greater than 5 on the WHO Clinical Progression Scale.
For the prospective study, able to give informed consent.
Not presenting an exclusion criterion
Exclusion Criteria:
Pregnancy
Patients with pre-existing terminal condition with life expectancy < 6 months
Patient with clinically frailty according to a score of the clinical frailty scale equal or superior to 7
Patients with pre-existing severe lung disease requiring home oxygen therapy.
Patients with pre-existing severe hepatic cirrhosis (Grade C according to the Child-Pugh classification)
Patients with pre-existing kidney failure (GFR strictly less than 15ml/min/1.73m2 according The KDIGO classification) or requiring renal replacement therapy.
Patients with pre-existing angle-closure glaucoma
Patient with symptomatic prostatic hypertrophy or bladder neck obstruction
Patient with history of seizure disorder
Patient with history of adverse reaction to antihistamines or to Cyproheptadine
Patients taking routinely SSRI or monoamine oxidase inhibitor therapy.
Patients presenting severe hepatic cytolysis with ALP >5 ULN at the time of study inclusion.
12. IPD Sharing Statement
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Pilot Study for Cyproheptadine in Hospitalized Patient for COVID-19
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