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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19 Pneumonia; Serotonin Syndrome; Platelet Dysfunction; Viral Pneumonia
• Intervention / Treatment: Drug: Cyproheptadine Hydrochloride 4 MG

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cyproheptadine

Drug: Cyproheptadine Hydrochloride 4 MG; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Approximately 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Approximately 28 days
Recruitement rate		6 month
Completion rate		6 month
Rate of Death from any cause		Approximately 28 days
Total number of days of hospitalisation		Approximately 28 days
Total number of days of hospitalization in the ICU		Approximately 28 days
Total number of days of mechanical ventilation		Approximately 28 days
Daily ROX ratio	Worst value of ROX ratio (SPO2/FiO2/Respiratory Rate) at D3,5,7,10,14,28	Approximately 28 days
Creatinine level	Worst value of Laboratory assessment of Creatinine at Days 3,5,7,10,14,28 after inclusion in the study	Approximately 28 days
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	Approximately 28 days
C Reactive Protein level	Worst value of Laboratory assessment of CRP at Days 3,5,7,10,14,28 after inclusion in the study	Approximately 28 days
D-Dimere level	Worst value of Laboratory assessment of D-Dimere at Days 3,5,7,10,14,28 after inclusion in the study	Approximately 28 days
Platelet count	Worst value of Laboratory assessment of platelet count at Days 3,5,7,10,14,28 after inclusion in the study	Approximately 28 days

Collaborators and Investigators

• Sponsor: Ciusss de L'Est de l'Île de Montréal

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): January 31, 2022

Study Registration Dates

• First Submitted: May 3, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Drug-Related Side Effects and Adverse Reactions; Carcinoid Tumor; COVID-19; Pneumonia; Pneumonia, Viral; Malignant Carcinoid Syndrome; Serotonin Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Cyproheptadine
• Other Study ID Numbers: 2022-2669

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No