Cyproheptadine in Severe COVID-19 : A Unblinded Randomized Trial

Sponsor

Ciusss de L'Est de l'Île de Montréal (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04820751

Collaborator

Covid-19 Early Treatment Fund (Other)

200

Enrollment

Arms

8.7

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Viral Pneumonia Serotonin Syndrome Platelet Dysfunction	Drug: Cyproheptadine Hydrochloride 4 MG	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cyproheptadine in Severe COVID-19 : A Unblinded Randomized Trial

Anticipated Study Start Date :

Apr 10, 2021

Anticipated Primary Completion Date :

Nov 1, 2021

Anticipated Study Completion Date :

Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyproheptadine and standard care 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	Drug: Cyproheptadine Hydrochloride 4 MG Cyproheptadine associated to standard care Other Names: Standard Care
No Intervention: Standard care Standard management of COVID-19 infection according to current international guidelines

Arm

Intervention/Treatment

Experimental: Cyproheptadine and standard care

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

Drug: Cyproheptadine Hydrochloride 4 MG

Cyproheptadine associated to standard care

Other Names:

Standard Care

No Intervention: Standard care

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

Outcome Measures

Primary Outcome Measures

Length of hospitalization [Through study completion, an average of 1 year]
Need mechanical ventilation (Non invasive or Invasive) [Through study completion, an average of 1 year]

Secondary Outcome Measures

Death [Day 28]
Length of hospitalization in the intensive care unit [Through study completion, an average of 1 year]
Duration of mechanical ventilation [Through study completion, an average of 1 year]
SOFA Score [At Day 1,3,5,7,10 after randomization]
Sequential Organ Failure Min Score 0-Max score 24 Higher scores mean a worse outcome
Heart rate [At Day 1,3,5,7,10 after randomization]
Respiratory Rate [At Day 1,3,5,7,10 after randomization]
Spo2/FiO2 and ROX ratio [At Day 1,3,5,7,10 after randomization]
CRP level [At Day 1,3,5,7,10 after randomization]
LDH level [At Day 1,3,5,7,10 after randomization]
D-Dimere level [At Day 1,3,5,7,10 after randomization]
Platelet count [At Day 1,3,5,7,10 after randomization]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women age 18 or older
Hospitalized and requiring medical care for COVID-19
Presenting respiratory failure cause by COVID 19 requiring oxygen and/or mechanical ventilation support
With radiographic evidence of pulmonary infiltrate
Able to give informed consent or, if unable to do so regarding the medical condition, having relatives able of consenting for the patient