Pilot Study for Cyproheptadine in Hospitalized Patient for COVID-19

COVID-19 Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04876573
• Other study ID #: 2022-2669
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 1, 2021
• Est. completion date: January 31, 2022

Study information

• Verified date: April 2021
• Source: Ciusss de L'Est de l'Île de Montréal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: January 31, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19 Pneumonia
• Malignant Carcinoid Syndrome
• Platelet Dysfunction
• Pneumonia
• Pneumonia, Viral
• Serotonin Syndrome
• Viral Pneumonia

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ciusss de L'Est de l'Île de Montréal

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Recruitement rate		6 month
Secondary	Completion rate		6 month
Secondary	Rate of Death from any cause		Approximately 28 days
Secondary	Total number of days of hospitalisation		Approximately 28 days
Secondary	Total number of days of hospitalization in the ICU		Approximately 28 days
Secondary	Total number of days of mechanical ventilation		Approximately 28 days
Secondary	Daily ROX ratio	Worst value of ROX ratio (SPO2/FiO2/Respiratory Rate) at D3,5,7,10,14,28	Approximately 28 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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