To Determine the Efficacy of Neurokinin 1 Receptor Antagonist as a Therapeutic Tool Against Cytokine Storm and Respiratory Failure in Covid-19 Patients

Study Overview
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Brief Summary
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This is a randomized, randomized controlled trial to investigate the efficacy and safety of Neurokinin-1 Receptor (NK-1R) 80 mg orally given daily to treat cytokine storm causing inflammatory lung injury and respiratory failure associated with severe or critical COVID-19 infection. NK-1R is the receptor of Substance P (SP) and responsible for its functionality. Here, we propose that SP via its tachykinin receptor, NK-1R may cause inflammation in Covid-19 infection. It may initiate the cytokine storming via binding to its receptor NK-1 and many inflammatory mediators are released. If SP release is reduced by NK-1R antagonist, it may control the cytokine storming and hence the hyper-responsiveness of the respiratory tract through reduction in cytokine storming It may serve as the treatment strategy for Covid-19 infected patients. Patients fulfilling the inclusion criteria will be enrolled after giving consent. They wll be randomized to treatment with either NK-1R antagonist or placebo in addition to Dexamethasone as a standard treatment given to both groups for Covid-19 infection as per the protocol at the treating hospital. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.

Detailed Description
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Objective: To evaluate the clinical outcomes of Neurokinin 1 Receptor antagonist in Covid-19 patients against the usual treatments as controls Dosage Aprepitant capsules may be given to patients from 3-5 days fosaprepitant dimeglumine (Injection 115mg, prodrug form of aprepitant) may be substituted for oral drug in case of critical patients May be taken with or without food Administration One capsule of Aprepitant once a day for 3-5 days

Official Title
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To Determine the Efficacy of Neurokinin 1 Receptor Antagonist as a Therapeutic Tool Against Cytokine Storm and Respiratory Failure in Covid-19 Patients

Conditions
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Neurokinin 1 Receptor, Substance P, Respiratory Illness, Inflammation, Covid-19, Coronavirus

Intervention / Treatment
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* Drug: NK-1R antagonist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 yrs Both genders Lab Confirmed COVID-19 infection by PCR or plasma positive of specific antibody against COVID-19 In hospital treatment ≥ 72 hours Admitted patients Severe Disease (Respiratory rate >=30/min; or (b) Rest SPO2<=90%; or (c) PaO2/FiO2<=300 mmHg) or Critical Phase (Respiratory failure and needs mechanical ventilation; or Shock occurs; or Multiple organ failure and needs ICU monitoring) Exclusion Criteria: Patients who are not willing to give consent known HIV,HBV, HCV infection pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>matching placebo drug | Drug: NK-1R antagonist<br>* NK-1R antagonist, 80 mg daily once for 3-5 days along with dexamethasone 6 mg daily for 5 days<br>|
| Experimental: NK-1R antagonist group<br>80 mg daily | Drug: NK-1R antagonist<br>* NK-1R antagonist, 80 mg daily once for 3-5 days along with dexamethasone 6 mg daily for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to improvement on a 7-point ordinal scale as compared to baseline |  | 14 days or discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total in-hospital days and the total duration |  | 14 days or discharge | 
| Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6) |  | 14 days or discharge | 
| Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples |  | 14 days or discharge | 
| Reduction from baseline of NRS for cough |  | 14 days or discharge | 
| Reduction from baseline of NRS for nausea |  | 14 days or discharge | 
| Time to normalization of fever for at least 48 hours |  | 14 days or discharge | 
| Time to improvement in oxygenation for at least 48 hours |  | 14 days or discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurokinin 1 receptor, Substance P, Respiratory illness, inflammation, Covid-19, Coronavirus