Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients With COVID-19

Phase 3

• Conditions: COVID-19 Pneumonia
• Interventions: Drug: Cyproheptadine

• Registration Number: NCT04979221
• Lead Sponsor: Hospital de Clinicas de Porto Alegre

Brief Summary

This randomized controled open label clinical trial conducted in patients with hypoxemic respiratory failure admitted to the ICU and requiring ventilatory support (invasive or non-invasive) is to evaluate whether treatment with cyproheptadine, a serotonin receptor antagonist, compared to usual care, increases the number of ventilator-free days.

Detailed Description

Some studies have shown increased platelet activation and reactivity in patients with COVID-19. This platelet activation is associated with serotonin release. Some characteristics observed during the evolution of COVID-19 may be associated with these increased levels of serotonin. In this scenario, the antagonism of the action of serotonin could improve the clinical course of patients affected by COVID-19. Cyprohepatdine is an anti-serotonergic antihistamine drug with a long track record of safety and tolerability.

Investigators will randomize 274 patients who have tested positive for COVID-19 and who will be admitted to the ICU requiring ventilatory support (invasive or non-invasive).

Patients will be randomized to a 1:1 ratio for receiving usual care + cyproheptadine (8mg three times a day for 10 days) or usual care.

Patients will be followed until discharge to determine length of stay in the ICU and hospital, mortality in the ICU and hospital and days free from ventilatory support during the first 28 days.

Study Timeline

• Status Verified: 2021-07
• Study First Submitted: 2021-07-23
• Study First Submitted QC: 2021-07-23
• Study Start: 2021-07-26
• Last Update Submitted: 2021-07-27
• Study First Posted: 2021-07-28
• Last Update Posted: 2021-08-03
• Primary Completion: 2022-01-26
• Study Completion: 2022-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 274

Inclusion Criteria

• Positive PCR for SARS-Cov-2
• ICU admission < 48 hours
• Age 18 years or older
• Need for invasive or non-invasive ventilatory support (non-invasive ventilation or high-flow nasal cannula) < 48 hours

Exclusion Criteria

• Pregnancy or breastfeeding
• Refusal to sign the informed consent form
• Expected death in the next 24 hours
• Patients taking routinely SSRI or monoamine oxidase inhibitor therapy
• Impossibility of using the enteral route
• History of seizure disorder
• History of adverse reaction to antihistamines or to cyproheptadine
• Readmission to the ICU

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyproheptadine and usual care	Cyproheptadine	Patients allocated to the intervention group will receive cyproheptadine within 6 hours after randomization, at a dose of 8mg every 8 hours for 10 days. Usual care (diagnostic testing, antibiotic administration, fluid resuscitation, hemodynamic management, and ventilatory support) will be applied in accordance with the clinical practice of each institution.

Primary Outcome Measures

Name	Time	Method
Ventilatory support	Day 28	Number of days free from ventiltory support during the first 28 days

Secondary Outcome Measures

Name	Time	Method
Length of stay in the intensive care unit	Through study completion, an average of 6 months
Hospital Mortality	Through study completion, an average of 6 months
Mechanical ventilation	Through study completion, an average of 6 months	Duration of mechanical ventilation
Mortality during 28 days	Day 28
Renal replacement therapy	Day 28
ICU Mortality	Through study completion, an average of 6 months
Length of stay in the hospital	Through study completion, an average of 6 months

Trial Locations

Locations (1)

Hospital de Clínica de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil