Clinical trial NCT04468646: To Determine the Efficacy of Neurokinin 1 Receptor Antagonist as a Therapeutic Tool Against Cytokine Storm and Respiratory Failure in Covid-19 Patients
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Neurokinin 1 Receptor, Substance P, Respiratory Illness, Inflammation, Covid-19, Coronavirus
Keywords: neurokinin 1 receptor
Substance P
Respiratory illness
inflammation
Covid-19
Coronavirus
Lead sponsor: University of Health Sciences Lahore
Sponsor class: OTHER
Collaborators: name: University of Lahore
name: Bahria International Hospital
First posted: 2020-07-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Time to improvement on a 7-point ordinal scale as compared to baseline
timeFrame: 14 days or discharge
Secondary outcomes:
measure: total in-hospital days and the total duration
timeFrame: 14 days or discharge
measure: Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6)
timeFrame: 14 days or discharge
measure: Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples
timeFrame: 14 days or discharge
measure: Reduction from baseline of NRS for cough
timeFrame: 14 days or discharge
measure: Reduction from baseline of NRS for nausea
timeFrame: 14 days or discharge
measure: Time to normalization of fever for at least 48 hours
timeFrame: 14 days or discharge
measure: Time to improvement in oxygenation for at least 48 hours
timeFrame: 14 days or discharge
Other outcomes:
Locations:
city: Lahore
country: Pakistan
facility: Bahria International Hospital
state: Punjab
Study officials:
References: