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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Drug: Cyproheptadine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyproheptadine and usual care<br>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. | Drug: Cyproheptadine<br>* Cyproheptadine 8mg three times a day during 10 days<br>|
| No Intervention: Usual care<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilatory support | Number of days free from ventiltory support during the first 28 days | Day 28 | 

Secondary Outcome Measures

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