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

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.

Study Overview

• Status: Unknown
• Conditions: Neurokinin 1 Receptor, Substance P, Respiratory Illness, Inflammation, Covid-19, Coronavirus
• Intervention / Treatment: Drug: NK-1R antagonist

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Pakistan
  • Punjab
    • Lahore, Punjab, Pakistan, 53720
      • Recruiting
      • Bahria International Hospital
      • Contact: Ahad Qayyum, MBBS,MRCP; Phone Number: 7 00924235340135; Email: lhrhospital@bahriatown.com.pk
      • Contact: Muhammad Asim o Rana, MBBS; Phone Number: 00923435807006; Email: lhrhospital@bahriatown.com.pk
      • Principal Investigator: Riffat Mehboob, PhD
      • Sub-Investigator: Fridoon Jawad Ahmad, PhD
      • Sub-Investigator: Ahad Qayyum, MBBS
      • Sub-Investigator: Muhammad Asim Rana, MBBS
      • Sub-Investigator: Javed Akram, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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
total in-hospital days and the total duration	14 days or discharge

Collaborators and Investigators

• Sponsor: Prof. Dr. Fridoon Jawad Ahmad
• Collaborators: University of Lahore; Bahria International Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 15, 2020
• Primary Completion (ANTICIPATED): July 15, 2020
• Study Completion (ANTICIPATED): August 30, 2020

Study Registration Dates

• First Submitted: July 7, 2020
• First Submitted That Met QC Criteria: July 10, 2020
• First Posted (ACTUAL): July 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2020
• Last Update Submitted That Met QC Criteria: July 10, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Covid-19; Coronavirus; inflammation; Substance P; neurokinin 1 receptor; Respiratory illness
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Systemic Inflammatory Response Syndrome; Shock; COVID-19; Coronavirus Infections; Inflammation; Respiratory Insufficiency; Cytokine Release Syndrome
• Other Study ID Numbers: UniversityHSL-NK1R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No