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

Sponsor

Prof. Dr. Fridoon Jawad Ahmad (Other)

Overall Status

Unknown status

CT.gov ID

NCT04468646

Collaborator

University of Lahore (Other), Bahria International Hospital (Other)

100

Enrollment

Location

Arms

2.5

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neurokinin 1 Receptor, Substance P, Respiratory Illness, Inflammation, Covid-19, Coronavirus	Drug: NK-1R antagonist	Phase 3

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 15, 2020

Anticipated Primary Completion Date :

Jul 15, 2020

Anticipated Study Completion Date :

Aug 30, 2020

Arms and Interventions

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

Arm

Intervention/Treatment

Placebo Comparator: Placebo

matching placebo drug

Drug: NK-1R antagonist

NK-1R antagonist, 80 mg daily once for 3-5 days along with dexamethasone 6 mg daily for 5 days

Experimental: NK-1R antagonist group

80 mg daily

Drug: NK-1R antagonist

NK-1R antagonist, 80 mg daily once for 3-5 days along with dexamethasone 6 mg daily for 5 days

Outcome Measures

Primary Outcome Measures

Time to improvement on a 7-point ordinal scale as compared to baseline [14 days or discharge]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)