| CTRI Number |
CTRI/2020/08/027162 [Registered on: 14/08/2020] Trial Registered Prospectively |
| Last Modified On: |
04/10/2021 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
A clinical study to understand the effect of Inosine Pranobex in Covid-19 patients when used along with the standard of Care in Covid patients. |
|
Scientific Title of Study
|
An Open-Label, Prospective, Randomized, Comparative, Parallel Group, Multi-Center, Proof of Concept Study to Assess the Efficacy and Safety of Inosine Pranobex Added to Current Standard of Care (CSC) in COVID-19 Patients. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| TML/IAD/2020/01 Version 1.1 24 Jul 2020 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Ashok Kumar Swain |
| Designation |
General Manager- Medical Services |
| Affiliation |
Themis Medicare Ltd |
| Address |
Floor 11/12, Udyog Nagar,S. V. Road, Goregaon (W),
Mumbai
Mumbai
MAHARASHTRA
400104
India |
| Phone |
9160255553 |
| Fax |
|
| Email |
ashok.swain@themismedicare.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Ashok Kumar Swain |
| Designation |
General Manager- Medical Services |
| Affiliation |
Themis Medicare Ltd |
| Address |
Floor 11/12, Udyog Nagar,S. V. Road, Goregaon (W),
Mumbai
Mumbai
MAHARASHTRA
400104
India |
| Phone |
9160255553 |
| Fax |
|
| Email |
ashok.swain@themismedicare.com |
|
Details of Contact Person
Public Query
|
| Name |
Mr Sangameshwar Iyer |
| Designation |
Company Secretary |
| Affiliation |
Themis Medicare Ltd |
| Address |
Floor 11/12, Udyog Nagar,S. V. Road, Goregaon (W),
Mumbai
Mumbai
MAHARASHTRA
400104
India |
| Phone |
9769692460 |
| Fax |
|
| Email |
sangameshwar.iyer@themismedicare.com |
|
|
Source of Monetary or Material Support
|
| Themis Medicare, 11/12, Udyog Nagar,
S. V. Road, Goregaon (W),
Mumbai – 400104,
Maharashtra, India |
|
|
Primary Sponsor
|
| Name |
Themis Medicare |
| Address |
11/12, Udyog Nagar,
S. V. Road, Goregaon (W),
Mumbai – 400104,
Maharashtra, India |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Ranganath T Ganga |
All India Institute of Medical Science |
Room No.1, Department of Pulmonary Medicine, All India Institute of Medical Science, Great Eastern Road, Tetibandha, Raipur
Raipur
CHHATTISGARH |
8004220308
ranganathtg@gmail.com |
| Dr Jayanthi C R |
Bangalore Medical College and Research Institute |
Room No. 1, Director Cabin, Bangalore Medical College and Research Institute, Fort KR Road, Bangalore
Bangalore
KARNATAKA |
9480832400
bmccrj@gmail.com |
| Dr Padmaja Saraf |
District Hospital, Chikalthana |
Room No.1, Department of Medicine, District Hospital Chikalthana, Aurangabad, Near Airport, Jalna Road, Aurangabad
Aurangabad
MAHARASHTRA |
9422216825
drpadmajasaraf@gmail.com |
| Dr Mohammad Siddiqui |
Heritage Institute of Medical Sciences |
Room No 1, Doctors Cabin, Heritage Institute of Medical Sciences, NH-2, GT Road Bypass, Varanasi
Varanasi
UTTAR PRADESH |
9889352598
drshafaatimam@gmail.com |
| Dr Mohd Saif Khan |
Rajendra Institutes of Medical Science |
Room No.1, RIMS CIR, Indraprasth Colony, Bariatu, Ranchi Jharkhand 834009
Ranchi
JHARKHAND |
8870561682
drsaif2k2@gmail.com |
| Dr Dnyaneshwar Halnor |
Vijay Vallabh Hospital and Medical Research Centre |
Room No. 423, Tirupati Nagar, Phase 1, Bolinj, Virar (West)
Mumbai (Suburban)
MAHARASHTRA |
7507779219
halnordnyanu@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Ethics Committee of Bangalore Medical College & Research Institute, Bangalore |
Approved |
| Ethics Committee of Ishwar Institute of Health Care, Aurangabad |
Approved |
| Ethics Committee, Rajendra Institute of Medical Sciences (RIMS) |
Approved |
| Heritage Institute of Medical Sciences Ethics Committee, Varanasi |
Approved |
| Vijay Vallabh Hospital and Medical Research Centre, Palghar |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Standard of Care |
Standard of Care as per Investigator discretion |
| Intervention |
Tab. Inosine Pranobex 500 mg in addition with Standard of Care |
[Synonyms of API: Inosine Acedoben Dimepranol (INN), Methisoprinol, Isoprinosine]
Dose: 500 mg
Route: Oral
Frequency: 2 Tabltes Four Times in a day. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1.Written signed and dated informed consent (patient or LAR).
2.Either gender, in the age group between 18 to 65 years
3.Patients of laboratory confirmed COVID-19 [nasopharyngeal (preferred) or oropharyngeal swab RT-PCR positive] presenting with WHO listed symptoms of COVID-19 c/o fever, headache, myalgia, cough, throat pain or shortness of breath
4.A score of between 3 to 5 on the WHO Modified Ordinal Scale for Clinical Improvement (refer protocol appendix 23.1)
5.SpO2 ≥90% for adults and respiratory rate ≤ 30/minute
6.Patients who provide a agree to abide by the study requirements |
|
| ExclusionCriteria |
| Details |
1.Known hypersensitivity to any of the ingredients of the study drug
2.Pregnant and lactating women
3.Children <18 yrs. of age; elderly >65 years
4.SpO2 <90% for adults and respiratory rate >30/minute
5.History of gout or hyperuricemia (serum uric acid level >6mg/dl), urolithiasis, nephrolithiasis or any degree of renal dysfunction
6.Patients with history of diagnosed primary congenital immunodeficiency, or acquired immunodeficiency like HIV, OR any Genetic or developmental anomaly like Cerebral Palsy, coeliac disease, lactose intolerant, cancer in nor remission stage.
7.Patient who are undergoing treatment with xanthine oxidase inhibitors, uricosuric agents, diuretics, immunosuppressive agents or zidovudine.
8.Patients with severe cardiac, hepatic, gastrointestinal, renal, pulmonary and skin diseases.
9.Patients simultaneously participating in another clinical study.
10.Medical or psychological conditions deemed by the investigators to interfere with successful participation in the study
11.A subject who is judged by the investigator as inappropriate to participate in the study for any reason other than those mentioned above |
|
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Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
An Open list of random numbers |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Percentage of patients with 2 points improvement or becoming asymptomatic (Grade 2 or less) on the modified WHO ordinal scale for clinical improvement between two groups at day 14 |
at Day 14 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Percentage of patients with 2 points improvement or becoming asymptomatic (Grade 2 or less) on the modified ordinal scale for clinical improvement for two groups at Day 7 and Day 21 |
Day 7 and Day 21 |
| Percentage of patients with Grade 1 on WHO modified ordinal scale confirmed (negative swab status) at Day 7, Day 14 and Day 21 for two treatment arms |
Day 7, 14 and 21 |
| Percentage of patients with Grade 2 on WHO modified ordinal scale at Day 7, Day 14 and Day 21 for two treatment arms |
Day 7, 14 and 21 |
| Time to two-point improvement or becoming asymptomatic (Grade 2 or less) on the modified WHO ordinal scale for patients in the two treatment arms |
NIL |
| Time to resolution of all clinical symptoms of COVID-19 viral infection (Grade 2 on WHO modified ordinal scale) for two treatment arms |
NIL |
| Time to RT-PCR swab negative COVID-19 viral infection (Grade 1 on WHO modified ordinal scale) for two treatment arms |
NIL |
| Mortality rate at Day 21 |
Day 21 |
| Severity of Dyspnea at Day 7, Day 14 and Day 21 |
Day 7, 14 and 21 |
| Time to discharge from hospital/duration of hospitalization for inpatients for two groups |
NIL |
| Rate of patients requiring oxygen/ventilation, and/or duration of oxygen use/duration of requiring ventilation for two groups at Day 7 and Day 14 |
Day 7 and 14 |
| Change in blood levels of NK cell, IL-6 and IL-10 between both treatment groups at Day 7, Day 14 and Day 21 visit. |
Day 7, 14 and 21 |
|
|
Target Sample Size
|
Total Sample Size="60"
Sample Size from India="60"
Final Enrollment numbers achieved (Total)= "83"
Final Enrollment numbers achieved (India)="83" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
20/08/2020 |
| Date of Study Completion (India) |
03/10/2020 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="2"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
Modification(s)
|
This is an open-label, prospective, comparative, multicentre proof of concept study. This multicentre study is to assess the effect of Tab. Inosine Pranobex as an add-on therapy to the standard of care for of patients in patients with confirmed acute COVID-19infection achieving clinical response, when compared to patients only on standard of care. Patients suggestive of RT-PCR [nasopharyngeal (preferred) and oropharyngeal swab positive] acute COVID-19 infection will be enrolled into this study with a score between 3 to 5 on the Modified Ordinal Scale for Clinical Improvement (refer protocol appendix 23.1). Both inpatient and outpatients will be enrolled into this study. The Modified WHO Ordinal Scale for Clinical Improvement, physical and systemic examination will be performed on a daily basis for inpatients and at the scheduled protocol visits for outpatients. The enrolled patients will receive Tab. Inosine Pranobex treatment for a period of 14 days. Patients will be assessed on day 7 (±1 day) and day 14 (±1 day). A follow-up safety assessment will be done on day 21 (±1 day). Croissance Clinical Research is providing the Data management Support to the clinical study. Summary of Results Primary Endpoint: Clinical Response (CR) at Day 14 was observed in 90% patients in IAD+CSC treatment arm vs. 85.37% patients in CSC treatment arm in the ITT population. The difference between the two treatments arms was not statistically significant (p-value: 0.526). Secondary Endpoints: CR at Day 7 and Day 21 in the IAD+CSC treatment arm and the CSC treatment arm was 57.50% vs. 43.90% (p-value: 0.221) and 90.00% vs. 87.80% (p-value: 0.753). The cumulative number of patients who achieved CR at day 10 in the IAD+CSC treatment group was 83% as compared 61% in CSC group (61%). Clinical Cure (CC) at Day 7, 14 and 21 in IAD+CSC treatment arm vs. CSC treatment arm in the ITT population was 57.50% vs. 43.90% (p-value: 0.221), 90.00% vs. 85.37% (p-value: 0.526) and 90.00% vs. 87.80% (p-value: 0.753), respectively. The cumulative number of patients who achieved CC at day 10 was 63% in the IAD+CSC group, as compared to 54% the CSC group. Virological Cure at Day 7, 14 and 21 in IAD+CSC treatment arm vs. CSC treatment arm in the ITT population was 37.50% vs. 34.15% (p-value: 0.753), 75.00% vs. 73.17% (p-value: 0.851) and 82.50% vs. 80.49% (p-value: 0.816), respectively. For the remaining secondary endpoints, there was no statistically significant difference between the two treatment groups for the ITT population. Sub-group analysis of patients showed that Inosine Pranobex, when added to standard of care containing Azithromycin and Hydroxychloroquine with or without Ivermectin, produced significantly higher clinical response (CR) at Day-14 than only standard of care (100.00% vs 69.23%; p=0.03). Overall, there was a trend of (numerically) higher CR, CC and VC on at Day 7, 14 and 21 in the IAD+CSC group compared to the CSC group; however, statistical significance could not be reached. This may be because of small sample size of the study variability in the current standard of care (CSC) among the different sites. There was no SAE and the drug was well tolerated. |