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Cyproheptadine

Histamine H1 Antagonists

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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.

Cyproheptadine Hydrochloride 4 MG

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.

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.

Pilot Study for Cyproheptadine in Hospitalized Patient for COVID-19

Pilot Study for Cyproheptadine in Hospitalized Patient for COVID-19: a Single-center, Observational Retrospective-prospective Comparative Study.

World Health Organisation Clinical Progression Scale for COVID 19 Minimal value 0 (uninfected) to maximal value 10 (Dead)

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

Worst value of ROX ratio (SPO2/FiO2/Respiratory Rate) at D3,5,7,10,14,28

Worst value of Laboratory assessment of Creatinine at Days 3,5,7,10,14,28 after inclusion in the study

Worst value of Laboratory assessment of Alanine amino transferase at Days 3,5,7,10,14,28 after inclusion in the study

Worst value of Laboratory assessment of CRP at Days 3,5,7,10,14,28 after inclusion in the study

Worst value of Laboratory assessment of D-Dimere at Days 3,5,7,10,14,28 after inclusion in the study

Worst value of Laboratory assessment of platelet count at Days 3,5,7,10,14,28 after inclusion in the study

Ciusss de L'Est de l'Île de Montréal

Start Cyproheptadine 8mg three times a day during 5 days. Dose will be reduced to 4mg three times a day if GFR inferior to 30ml/min/1.73m²

Standard management of COVID-19 infection according to current international guidelines

Standard management of COVID-19 infection according to current international guidelines

Cyproheptadine associated to standard care

Philippe Rola, MD

Alexandre Noel, MD

This randomized controled open label clinical trial is to evaluate the effect of Cyproheptadine on the clinical course of patients presenting a severe SARS-COV 2 pneumonia.

Observational and biochemical studies have identified an interesting pathway in the pathophysiology of certain clinical-biological characteristics of COVID-19, linked to an excess of serotonin. We hypothesize that the antagonism of the action of serotonin could improve the clinical course of patients most severely affected by COVID-19.

One such antagonist of serotonin with a long track record of safety and tolerability is cyproheptadine. Cyproheptadine acts as an antagonist of 5-hydroxytryptamine (5HT=serotonin) receptor subtype 2 as well as histamine-1 receptor. Many of the potent effects of serotonin on lung vascular tone, respiratory rate, and systemic vascular beds are mediated by 5-HT receptor subtype 2.

Investigators will randomize approximately 200 participants, aged 18 and older, who have tested positive for COVID-19 and who will be hospitalized at Santa Cabrini Hospital in Montreal, Quebec, Canada, presenting a severe form of covid-pneumonia-19 requiring supplemental oxygen.

Study eligibility of all participants will be assessed first. Once a participant is confirmed eligible and consented, they will participate in the study.

Participants will be randomly assigned (1: 1) to either take cyproheptadine 8 mg by mouth three times a day for 5 days and receive standard care or receive standard care alone.

The dose will be adjusted according to the glomerular filtration rate.

On D1, D3, D5, D7 and D10 since randomization, participant's vital signs (including SpO2, respiratory rate, FiO2 or oxygen flow, heart rate, blood pressure and temperature), blood creatinine, bilirubin, CRP, LDH, Dimers and platelets the count will be evaluated. Any adverse event will be assessed daily and documented.

Cyproheptadine in Severe COVID-19 : A Unblinded Randomized Trial

Sequential Organ Failure Min Score 0-Max score 24 Higher scores mean a worse outcome

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pilot Study for Cyproheptadine in Hospitalized Patient for COVID-19	NCT04876573	Viral Pneumonia COVID-19 Pneumo... Serotonin Syndr... Platelet Dysfun...	Cyproheptadine ...	18 Years -	Ciusss de L'Est de l'Île de Montréal
Cyproheptadine in Severe COVID-19 : A Unblinded Randomized Trial	NCT04820751	Viral Pneumonia Serotonin Syndr... Platelet Dysfun...	Cyproheptadine ...	18 Years - 99 Years	Ciusss de L'Est de l'Île de Montréal

Spots Global Cancer Trial Database for viral pneumonia