Clinical trial NCT04876573: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Viral Pneumonia
COVID-19 Pneumonia
Serotonin Syndrome
Platelet Dysfunction
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
First posted: 2021-05-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical evolution according the WHO Clinical Progression Scale
timeFrame: Approximately 28 days
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Approximately 28 days
measure: Recruitement rate
timeFrame: 6 month
measure: Completion rate
timeFrame: 6 month
measure: Rate of Death from any cause
timeFrame: Approximately 28 days
measure: Total number of days of hospitalisation
timeFrame: Approximately 28 days
measure: Total number of days of hospitalization in the ICU
timeFrame: Approximately 28 days
measure: Total number of days of mechanical ventilation
timeFrame: Approximately 28 days
measure: Daily ROX ratio
timeFrame: Approximately 28 days
measure: Creatinine level
timeFrame: Approximately 28 days
measure: Alanine amino transferase level
timeFrame: Approximately 28 days
measure: C Reactive Protein level
timeFrame: Approximately 28 days
measure: D-Dimere level
timeFrame: Approximately 28 days
measure: Platelet count
timeFrame: Approximately 28 days
Other outcomes:
Locations:
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