FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2020/07/026529 [Registered on: 13/07/2020] Trial Registered Prospectively
Last Modified On: 13/07/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   A Study to evaluate the safety and efficacy of Eflornithine against the standard of care in human adult hospitalized COVID-19 patients 
Scientific Title of Study   An open label, randomized, three treatment, three arm, parallel group, investigator initiated, comparative clinical trial to evaluate the safety and efficacy of Eflornithine against the standard of care in human adult hospitalized COVID-19 patients 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Abhay Vispute Shantaram 
Designation  Director and physician 
Affiliation  SRV Hospital 
Address  Medicine department SRV Hospital Dr Mandakini Parihar Marg opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra

Mumbai
MAHARASHTRA
400089
India 
Phone  9819428656  
Fax    
Email  drasv@rediffmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Abhay Vispute Shantaram 
Designation  Director and Physician 
Affiliation  Dept. of Medicine, SRV Hospital 
Address  SRV Hospital Dr Mandakini Parihar Marg opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra

Mumbai
MAHARASHTRA
400089
India 
Phone  9819428656  
Fax    
Email  drasv@rediffmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Abhay Vispute Shantaram 
Designation  Director and Physician 
Affiliation  Dept. of Medicine, SRV Hospital 
Address  SRV Hospital Dr Mandakini Parihar Marg opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra

Mumbai
MAHARASHTRA
400089
India 
Phone  9819428656  
Fax    
Email  drasv@rediffmail.com  
 
Source of Monetary or Material Support  
Dept. of Medicine, SRV Hospital, Dr Mandakini Parihar Marg, opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra 400089 
 
Primary Sponsor  
Name  Dr Abhay Vispute Shantaram 
Address  SRV Hospital Dr Mandakini Parihar Marg, opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra 400089 
Type of Sponsor  Other [Self] 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Abhay Vispute Shantaram  SRV Hospital  Dept. of Medicine Dr Mandakini Parihar Marg, opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur 400089
Mumbai
MAHARASHTRA 
9819428656

drasv@rediffmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
New Healthcare Nursing Home  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  B972||Coronavirus as the cause of diseases classified elsewhere, B998||Other infectious disease,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Eflornithine  Treatment arm 1: Dose 2.5g, Oral solution administered every 6 hours + Standard of Care (SoC) excluding antimalarials and antivirals Treatment arm 2: Dose 5.0, oral solution administered every 6 hours + Standard of Care (SoC) excluding antimalarials and antivirals.  
Comparator Agent  Standard Of Care (SoC)  SoC including antimalarials, antivirals and macrolides. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  85.00 Year(s)
Gender  Both 
Details  1. Has laboratory-confirmed positive COVID-19 infection as determined by RT-PCR or other commercial or public health assay in any specimen, an RT-PCR (Nasopharynx and Throat) test shall be repeated to assess eligibility.
2. Symptomatic male or non-pregnant female adult requiring hospitalization, with or without comorbidities between the age group of 18-85 years of age at time of enrollment.
3. Illness or condition of any duration, and at least one of the following:
- Fever defined as temperature greater than or equal to 36.6C (98.4F) measured by an infrared body temperature detection device.
- Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
- Clinical assessment (evidence of rales/crackles on exam) AND SpO2 less than or equal to 94% on room air, OR
- Requiring supplemental oxygen, OR
- Requiring mechanical ventilation.
4. Women of childbearing potential must agree to either abstain or use at
least one primary form of contraception not including hormonal contraception from the time of screening to the end of study (Day 28 or live hospital discharge, whichever is earlier).
5. Agrees to not participate in another clinical trial for the treatment of COVID-19 until the end of study (Day 28 or live hospital discharge, whichever is earlier).
6. Subject (or legally authorized representative) providing written informed consent prior to initiation of any study procedures.
7. Has a personal (mobile/cellular) phone, and is able to nominate at least one locator individual (e.g. a family member, friend or recovery mentor) with a verifiable address and a telephone number to assist with the arrangement of follow-up appointments as required.
 
 
ExclusionCriteria 
Details  1. Testing positive for HIV, HbsAg and HCV infection.
2. Females who are currently pregnant or breastfeeding.
3. Allergy or other contraindication to one of the investigational products.
4. Has received Eflornithine within the last 10 days.
5. Has received anti-viral, anti-malarial or anti-bacterial within the last 14
days.
6. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST)
> 5 X upper limit of normal (ULN).
7. QTc interval ≥ 500ms.
8. Recent Myocardial Infarction (within last 6 months).
9. Known case of (K/C/O) Congestive heart failure.
10. K/C/O Chronic Kidney Disease.
11. K/C/O active Tuberculosis.
12. History of drug or alcohol dependence in the past 6 months.
13. In the opinion of the clinical team, progression to death is imminent and
inevitable within the next 24 hours, irrespective of the provision of
treatments.
14. Anticipated transfer to another hospital which is not a study site within
72 hours.
15. K/C/O of epilepsy. 
 
Method of Generating Random Sequence   Stratified block randomization 
Method of Concealment   An Open list of random numbers 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Time to Negative Viral Test: will be assessed by the time taken from initiation of the study treatment (i.e. the first study dose) to the day when the RT-PCR test results are first shown to be negative from samples collected from all of the below:
a) Nasopharynx
b) Throat
An ICMR approved RT-PCR test resulting negative in the first instance, will be reconfirmed ≥ 24 hours apart with fresh samples from the same sites (a) Nasopharynx and (b) Throat. 
1, 4, 7, 14, 21 and 28 days
 
 
Secondary Outcome  
Outcome  TimePoints 
1. Time to Clinical Improvement (TTCI)
2. Eight-point ordinal 14-day analysis
3. Eight-point ordinal 28-day analysis
4. Oxygen free days
5. Duration of hospitalization in survivors and non-survivors
6. Subject 14-day mortality
7. Subject 28-day mortality
8. Time to death
9. Percentage Change in Biochemical Analysis
Safety Endpoints:
i) Cumulative incidence of Grade 3 and 4 adverse events (AEs) and Serious Adverse Events (SAEs)
ii)Cumulative incidence of Hearing Impairment 
1, 4, 7, 14, 21 and 28 days 
 
Target Sample Size   Total Sample Size="18"
Sample Size from India="18" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2/ Phase 3 
Date of First Enrollment (India)   20/07/2020 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="0"
Months="3"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   Will be published in Pubmed indexed journal 
Brief Summary  

Based on the fact that Eflornithine has shown in vitro viral load reduction in MERS-CoV, it is hypothesized that the primary efficacy endpoint (time to viral load clearance by way of a negative RT-PCR test for COVID-19 infection) in patients of the Eflornithine treatment arms (Arms 1 & 2) will be statistically superior to the comparator arm (Arm 3) wherein the patient will receive antimalarials/ antivirals/ macrolides as a part of standard of care.

Further, it is hypothesized that the primary efficacy endpoint (time to viral load clearance by way of a negative RT-PCR test for COVID-19 infection) in patients of the Eflornithine treatment arm 2 will be statistically superior to the treatment arms 1.

It is also hypothesized that the Eflonrithine treatment arms (Arms 1 & 2) will have a faster time to clinical improvement, a fewer incidence of deaths on day 14 & 28, a lesser duration of hospitalization and more number of oxygen free days as compred to the comparator arm (Arm 3).

It is also hypothesized that the Eflonrithine treatment arm 2 will have a faster time to clinical improvement, a fewer incidence of deaths on day 14 & 28, a lesser duration of hospitalization and more number of oxygen free days as compred to the treatment arm 1. 

Treatment arm 1: Eflornithine Granules (2.5 g) (Orange Flavour; Sugar Free) for oral solution administered every 6 hours + Standard of Care (SoC) excluding antimalarials and antivirals.

Treatment arm 2: Eflornithine Granules (5.0 g) (Orange Flavour; Sugar Free) for oral solution administered every 6 hours + Standard of Care (SoC) excluding antimalarials and antivirals.

Treatment arm 3: SoC including antimalarials, antivirals and macrolides.

Standard of Care during the Study will be as per the current guidelines “Revised Guidelines on Clinical Management of COVID – 19” issued by Government of India, Ministry of Health & Family Welfare (MOHFW), Directorate General of Health Services (EMR Division) (Government of India) dated 31st March 2020[1]. The use of antimalarials and antivirals will be excluded as a part of SoC for treatment arms 1 and 2 only. Treatment arm 3 however, may include use of these classes of drugs as per the MOHFW guidelines or as per the local written hospital policy.

Study design has been labeled as investigator initiated trial, a sample size of 6 patients per arm has been considered. Since the primary and secondary endpoints are independent of patient feedback or investigator assessment, no bias is anticipated and hence an open label design has been proposed. The outcome measures are purely based on laboratory results and factual observations (death, oxygen free days, duration of hospitalization) and have a no risk of bias. As the safety of the study drug has been already established and the drug is already in market in other finished dosage forms and for other indications. Considering dose determination as the main object, in this trial three doses of Eflornithine granules (2.5 g or 5.0 g) is comparing with standard of care, to evaluate the efficacy and ensuring the safety. 

Patients enrolled in the study will receive Standard of Care (SoC). Standard of care for treatment arms 1 and 2 will exclude antimalarials and antivirals. However, pateints randomized in treatment arm 3 will receive SoC which includes antimalarials and antivirals as required. 

 
Close