FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2020/06/026001 [Registered on: 21/06/2020] Trial Registered Prospectively
Last Modified On: 07/09/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study
Modification(s)  
Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   Ivermectin in COVID 
Scientific Title of Study   Randomised Controlled Trial of Ivermectin in hospitalised patients with COVID19 
Trial Acronym  RIVET-COV 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Anant Mohan 
Designation  Professor and Head 
Affiliation  AIIMS New Delhi 
Address  Third Floor,Porta Cabin, Department of Pulmonary, Critical Care And Sleep Medicine, AIIMS New Delhi

New Delhi
DELHI
110029
India 
Phone    
Fax    
Email  anantmohan@yahoo.com  
 
Details of Contact Person
Scientific Query
 
Name  Anant Mohan 
Designation  Professor and Head 
Affiliation  AIIMS New Delhi 
Address  Third Floor,Porta Cabin, Department of Pulmonary, Critical Care And Sleep Medicine, AIIMS New Delhi

New Delhi
DELHI
110029
India 
Phone    
Fax    
Email  anantmohan@yahoo.com  
 
Details of Contact Person
Public Query
 
Name  Anant Mohan 
Designation  Professor and Head 
Affiliation  AIIMS New Delhi 
Address  Third Floor,Porta Cabin, Department of Pulmonary, Critical Care And Sleep Medicine, AIIMS New Delhi

New Delhi
DELHI
110029
India 
Phone    
Fax    
Email  anantmohan@yahoo.com  
 
Source of Monetary or Material Support  
All India Institute of Medical Sciences New Delhi 
 
Primary Sponsor  
Name  AIIMS New Delhi 
Address  Third Floor,Porta Cabin, Department of Pulmonary, Critical Care And Sleep Medicine, AIIMS New Delhi 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
All India Institute of Medical Sciences New Delhi  AIIMS, Ansari Nagar East, New Delhi India 110029 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Anant Mohan  AIIMS New Delhi and AIIMS NCI Jhajjar  Room No 2 Third Floor New Private Ward AIIMS Ansari Nagar East New Delhi 110029
New Delhi
DELHI 
01126593488

anantmohan@yahoo.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 2  
Name of Committee  Approval Status 
Institute Ethics Committee  Approved 
Institute Ethics Committee  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,  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Intervention  Intervention Arm 1  12 mg (200 microgram/kg) Formulation: elixir Route of administration: oral Frequency: Only single dose 
Intervention  Intervention Arm 2   24 mg (400 microgram/kg) Formulation: elixir Route of administration: oral Frequency: Only single dose 
Comparator Agent  Placebo  placebo Formulation: Elixir of similar taste and consistency Frequency: only single dose alongwith Standard medical care as per treating physician and institution 
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  diagnosed COVID19 patients admitted to AIIMS COVID facility
Age > 18 years
Informed consent
Non-severe disease: Non-severe disease (Asymptomatic/ Mild
disease OR moderate): SpO2≥90% on room
air with presence of clinical features of
dyspnea and/or hypoxia, fever, cough and/or
Respiratory Rate more or equal to 24 per
minute 
 
ExclusionCriteria 
Details  Not giving written informed consent
ALT/AST >5 times the upper limit of normal.
Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30).
Pregnant or breast feeding.
Allergy to any study medication.
Severe co-morbidity as per investigator’s assessment
Comorbid condition like myocardial infarction or heart failure within 90 days of recruitment.
Prolonged QT interval (>450 ms)
Any other concomitant therapeutic trial
Weight <15 kg
 
 
Method of Generating Random Sequence
Modification(s)  
Stratified block randomization 
Method of Concealment
Modification(s)  
Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking
Modification(s)  
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded 
Primary Outcome
Modification(s)  
Outcome  TimePoints 
To evaluate the efficacy of ivermectin in
reducing viral load estimated by RTPCR
cycle threshold at day 5 after drug
administration in patients with COVID19 
Day 5 after drug administration 
 
Secondary Outcome
Modification(s)  
Outcome  TimePoints 
Time to clinical resolution in study group as compared to standard care  till discharge or death 
Clinical status of subject at week 2 (on a 7-point ordinal scale) as follows: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Death.  Week 2 
Frequency of clinical worsening in study group as compared to standard care   till discharge or death 
Qualitative and quantitative PCR for SARS CoV-2 in pharyngeal swab on days 0, 3, 5,
and 7 (while hospitalized) in both arms 
days 0, 3, 5, and 7 (while hospitalized)
 
Frequency of serious adverse events in study
group as compared to standard care 
till death or discharge 
 
Target Sample Size
Modification(s)  
Total Sample Size="90"
Sample Size from India="90" 
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)   25/06/2020 
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="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   Nil 
Brief Summary
Modification(s)  

In December 2019 outbreak of cases of Pneumonia of unknown etiology were identified in Wuhan city in Hubei province of China. By 7th January 2020 the Chinese authorities identified a new strain of coronavirus which was later named as 2019 novel coronavirus (2019-nCoV). By 30th January 2020, the World Health Organization (WHO) declared the outbreak as Public Health Emergency of International Concern. Since then the cases of viral pneumonia associated with this strain have gripped almost all countries of the world.  WHO subsequently declared COVID19 as pandemic on 11th March 2020. As per WHO data, as on 17th April 2020 the overall cases worldwide are 2,074529 with 139,378 deaths attributed to this viral illness. Countries like US, Spain, Italy and France are having the maximum burden of this illness.

There is no efficacious treatment for the disease till date. Proposed drugs with potential efficacy can be broadly categorised into 4 classes, i.e., (a) Anti-viral  and  Anti-inflammatory drugs,  (b)  Anti-malaria  drugs,  (c) Traditional  Chinese  drugs  (TCM)  and  (d)  other treatments/drugs.    Small clinical trials have demonstrated the effect of hydroxychloroquine on viral clearance.(4) However, there are reports of cardiotoxicity and lack of benefit in severe disease.  As of today, hydroxychloroquine with or without azithromycin is not being recommended by any of the major international societies or national guidelines for treatment.  Ritonavir-lopinavir did not achieve its primary endpoint in a recently published randomized controlled trial, even though it did reduce duration of mechanical ventilation and other secondary outcomes. Similarly, there are encouraging reports with use of remdesivir, but there are concerns regarding patient selection in its use.  Other experimental therapies like plasma exchange, convalescent plasma and interferon therapy are being studied.

 

We postulate that single dose ivermectin given early in the course of infection, will result in decreased viral load, that will translate into lesser number of days that a patient remains infective, which will, in turn, reduce basic reproduction number (R0) for COVID19.  Also, as high viral load has been correlated with complications in later course, there is potential to reduce progression to severe disease and complications.  Another interesting aspect is that ivermectin is best suited to mass treatment in suspected COVID19 cases, as it has been tried in mass prophylaxis programs in other diseases like leishmaniasis. As it is in essential drug list, if found useful, its use would also be cost effective.


We have performed a pharmacokinetic modelling study, and based on available pharmacokinetic data, and virucidal concentrations used in the in-vitro study, we have calculated that the required dose of ivermectin for achieving the peak plasma level, and also the area under curve for majority of elimination half-life, is 96 mg (1600 mg/kg), with an estimated half-life of around 60 hours (personal observation, submitted for publication). However, a dose ranging study in COVID patients is important to decide regarding safe and effective dose.


 
Close