CTRI Number |
CTRI/2020/06/026220 [Registered on: 29/06/2020] Trial Registered Prospectively |
Last Modified On: |
20/10/2020 |
Post Graduate Thesis |
No |
Type of Trial |
Interventional |
Type of Study
|
Drug |
Study Design |
Randomized, Parallel Group Trial |
Public Title of Study
|
A study to evaluate the efficacy and safety of Nafamostat Mesilate in treatment of Coronavirus infection |
Scientific Title of Study
|
An Open Label, Randomized, Multicenter, Controlled Clinical Study to Evaluate the Efficacy and Safety of Nafamostat Mesilate in the Treatment of Moderate COVID-19 Disease |
Trial Acronym |
|
Secondary IDs if Any
|
Secondary ID |
Identifier |
ICR/20/004, Version No. 1.0; Dated 23/APR/2020 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
Name |
Dr Shilpi Dhawan |
Designation |
Head India Clinical Research |
Affiliation |
Sun Pharma Laboratories Limited |
Address |
Sun Pharma Laboratories Limited,
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India.
Mumbai MAHARASHTRA 400063 India |
Phone |
02243245299 |
Fax |
02243244343 |
Email |
shilpi.dhawan@sunpharma.com |
|
Details of Contact Person Scientific Query
|
Name |
Dr Maulik Doshi |
Designation |
Medical Monitor |
Affiliation |
Sun Pharma laboratories Limited |
Address |
Sun Pharma laboratories Limited
Tandalja, Vadodara-390020
Gujarat
Vadodara GUJARAT 390020 India |
Phone |
02656612829 |
Fax |
02652354897 |
Email |
maulik.doshi@sunpharma.com |
|
Details of Contact Person Public Query
|
Name |
Guruprasad Palekar |
Designation |
Deputy General Manager |
Affiliation |
Sun Pharma Laboratories Limited |
Address |
Sun Pharma Laboratories Limited
Sun House,
201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400063
Mumbai MAHARASHTRA 400063 India |
Phone |
02243246215 |
Fax |
02243244343 |
Email |
guruprasad.palekar@sunpharma.com |
|
Source of Monetary or Material Support
|
Sun Pharmaceutical Industries Limited
Sun House,
201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400063
|
|
Primary Sponsor
|
Name |
Sun Pharmaceutical Industries Limited |
Address |
Sun Pharmaceutical Industries Limited
Sun House,
201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400063
|
Type of Sponsor |
Pharmaceutical industry-Indian |
|
Details of Secondary Sponsor
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
No of Sites = 7 |
Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
Dr SAMDANI PRATIT PRAHALAD |
Bhatia Hospital |
Ground Floor, G-1, Department of Medicine, Bhatia Hospital,Taerdeo Road, Old Chikhlawadi, Grant Road , (W), Tardeo, Mumbai-400007, Maharashtra, India Mumbai MAHARASHTRA
Mumbai MAHARASHTRA |
9322589110
drpratit@gmail.com |
Dr SAMDANI PRATIT PRAHALAD |
Bhatia Hospital |
Ground Floor, G-1,
Department of
Medicine, Bhatia
Hospital,Taerdeo Road,
Old Chikhlawadi, Grant
Road , (W), Tardeo,
Mumbai-400007,
Maharashtra, India Mumbai MAHARASHTRA |
9322589110
drpratit@gmail.com |
Dr Ajit Avhad |
Family Care Hospitals |
P.K. Road, Opp Seven Square Academy, Mira road east, Thane, Maharashtra - 401107 Mumbai MAHARASHTRA |
8007667576
ajitgorakshavhad@gmail.com |
Dr Bhattacharya Meenakshi |
Government Medical College and Hospital |
Second Floor, Department of Medicine, Government Medical College and Hospital, Aurangabad, Panchakki Road, Aurangabad. 431001 Aurangabad MAHARASHTRA Aurangabad MAHARASHTRA |
9922931527
mabhattacharya@gmail.com |
Dr Jhaveri Ajay Bharat |
Kasturba Hospital for Infectious Diseases |
RMO Room, Ground floor, Next to Medical Superintendant Office, Kasturba Hospital for Infectious Diseases, Sane Guruji Marg, Mumbai, 400011 Mumbai MAHARASHTRA
Mumbai MAHARASHTRA |
9867433330
drajayjhaveri@gmail.com |
Dr MRS GIRIJA NAIR |
Padmashree Dr D Y Patil Medical College Hospital & Research Center |
1st Floor OPD 69 Department of Pulmonary Medicine Padmashree Dr D Y Patil Medical College Hospital & Research Center, Plot No. 2 Sector 5,Nerul,Navi Mumbai 400706 Mumbai MAHARASHTRA |
9324294457
girijapn@hotmail.com |
Dr Halnor Dnyaneshwar Machhindra |
Vijay Vallabj Hospital and Medical Research Center |
Vijay Vallabh Hospital and Medical Research Center, Room No. 405, Clinical Research Department, 4th floor, Plot No. 423, Tirupati Nagar, Phase 1, Bolinj, Virar (West), Distt-Palghar, Pincode - 401303 Mumbai MAHARASHTRA |
7507779219
halnordnyanu@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
No of Ethics Committees= 7 |
Name of Committee |
Approval Status |
BHATIA HOSPITAL MEDICAL RESEARCH SOCIETY EC |
Approved |
Ethics Committee Jaslok Hospital and Research Center |
Approved |
Institutional Ethics Committee, D Y Patil Medical College |
Approved |
Institutional Ethics Committee, GGMC, Mumbai |
Approved |
Institutional Ethics Committee, Vijay Vallabh Hospital |
Approved |
Institutional Ethics Committee, Vijay Vallabh Hospital |
Approved |
Institutional Ethics Committee; Government Medical College Aurangabad |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
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 |
Intervention |
Nafamostat Mesilate Injection 50 mg/ 100 mg vial |
Dissolve a daily dose of Nafamostat mesilate in 1000 ml of 5 % dextrose and to be infused at dose of 0.1 mg/kg/hr for 24 hrs by continuous infusion for 10 days
If the patient meets clinical improvement/ discharge criteria any time prior to completing infusion on Day 10, the treatment can be stopped earlier and subject can be discharged and followed up as defined in protocol
Also, Standard of care as per institutional practice.
Patients may be given prophylactic LMWH (e.g., Enoxaparin 1mg/kg per day Subcutaneously) as per investigator’s discretion. Before starting LMWH, investigator should check for bleeding tendency riskand presence of any contraindications. When Nafamostat and LMWH are given concomitantly daily PT/INR and aPTT should be monitored. |
Comparator Agent |
Standard of care as per institutional practice |
Standard of care as per institutional practice
Patients may be given prophylactic LMWH (e.g., Enoxaparin 1mg/kg per day Subcutaneously) as per investigator’s discretion. Before starting LMWH, investigator should check for bleeding tendency riskand presence of any contraindications. When Nafamostat and LMWH are given concomitantly daily PT/INR and aPTT should be monitored. |
|
Inclusion Criteria
|
Age From |
18.00 Year(s) |
Age To |
65.00 Year(s) |
Gender |
Both |
Details |
Subjects will be included in the study if they meet all of the following criteria:
1. Male or non-pregnant, non-lactating female patient aged ≥ 18 and ≤ 65 years
2. Patient presenting with symptoms of fever (axillary ≥ 98.6°F or oral ≥ 99.5°F) with
cough/shortness of breath
3. Patient with Moderate COVID -19 infection meeting the clinical criteria of (note) -
a. Pneumonia (confirmed on chest imaging) and
b. Respiratory rate 15 to 30 breaths/minute (both inclusive) and
c. Oxygen saturation- SpO2 90%-94% (both inclusive) on room air OR PaO2/ FiO2: 200-
300 mmHg (both inclusive)
4. Patient with RT-PCR confirmed diagnosis of COVID-19
5. Patient randomized within 72 hours of diagnosis of pneumonia
6. Patient who provides written informed consent and agrees to comply with study procedures
7. Women of childbearing potential must have a negative urine pregnancy test prior to study entry
as per MOHFW guideline
Note: (https://www.mohfw.gov.in/pdf/FinalGuidanceonMangaementofCovidcasesversion2.pdf) |
|
ExclusionCriteria |
Details |
Patient will be deemed ineligible to participate in the study if he/she fulfils any of the following criteria:
1 Patient requiring extracorporeal membrane oxygenation (ECMO) or invasive ventilation
2 Patient with multiple organ failure requiring ICU monitoring and the treatment
3 Patient with rapidly deteriorating clinical condition or low likelihood to complete the study according to the investigator
4 Patient with eGFR < 30 ml/min/m2 assessed with CKD EPI formula
5 Patient with Pre-existing renal failure on hemodialysis or peritoneal dialysis requiring renal replacement therapy
6 Patient with Current or chronic history of liver disease (Child Pugh score ≥ 10), or known hepatic or biliary abnormalities
7 Patient with known active hepatitis, tuberculosis and definite bacterial or fungal infections
8 Patient with history of chronic interstitial lung disease on imaging
9 Patient with history of hospitalization for respiratory failure within the past six months
10 Patient with history of chronic vascular disease resulting in severe exercise restriction (i.e. unable to
perform household duties)
11 Patient with history of secondary polycythemia, severe pulmonary hypertension, or ventilator dependency
12 Patient with history of vasculitis with diffuse alveolar hemorrhage
13 Patient with severe active bleeding at screening or with bleeding tendency (platelet count < 50,000/ul, INR ≥ 3, aPTT > 65 seconds)
14 Patient with diabetes
15 Patient with any concurrent medical condition or uncontrolled, clinically significant systemic disease [e.g., heart failure (NYHA III/IV), COPD, hypertension (≥ 160/100 mm Hg), chronic respiratory failure, anaemia (≤ 8 g/dl) etc.) that, in the opinion of the Investigator precludes the subject’s participation in the study or interferes with the interpretation of the study results
16 Patient with history of serology tests positive for hepatitis B or hepatitis C or human immunodeficiency virus
17 Patient with altered mental state
18 Patient with history of retinopathy or macular degeneration
19 Patient with history of glucose-6-phosphate dehydrogenase (G6PD) deficiency
20 Patient with prolonged QTc-interval at baseline ECG (>450 ms in males or > 470 ms in females)
21 Patient taking concomitant medication associated with QTc-interval prolongation, which cannot be withdrawn prior to study drug administration
22 Patient requiring high doses of loop diuretics (i.e. > 240 mg furosemide daily) with significant intravascular volume depletion, as assessed clinically
23 Patient taking immunosuppressive treatment
24 Patient having history of sensitivity to heparin or heparin-induced thrombocytopenia
25 Patient with history of hypersensitivity towards any drug of standard of care or Nafamostat including their excipients
26 Patient who participated in a clinical trial with an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
27 Patient participated in trials for COVID-19 within 30 days before screening
28 Patient with hyperkalemia , i.e. serum K+ levels > 5.0 mEq/L
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
Method of Concealment
|
An Open list of random numbers |
Blinding/Masking
|
Not Applicable |
Primary Outcome
|
Outcome |
TimePoints |
Proportion of patients showing clinical improvement |
by Day 14 |
|
Secondary Outcome
|
Outcome |
TimePoints |
Proportion of patients showing clinical improvement |
by Day 7 and Day 28 |
Time to clinical improvement |
upto Day 28 |
Time to improvement of lung imaging |
upto Day 28 |
Percent change in 24 hour PaO2/FiO2 ratio on days 7, 14, Day of discharge compared to baseline |
Day 7, Day 14 and Day of Discharge |
Time to normalization of fever without use of antipyretics in last 24 hours |
upto Day 28 |
Time to first negative SARS-CoV-2 RT-PCR in upper or lower respiratory tract specimen |
upto Day 28 |
Duration (days) of supplemental oxygen therapy |
upto Day 28 |
Proportion of patients showing deterioration of clinical condition as assessed by at least 1 point worsening on 7 point ordinal scale (non-invasive ventilation, mechanical ventilation, ECMO or death) |
Day 14, Day 28 |
Number of deaths (All cause mortality) |
upto Day 28 |
Safety evaluation, as measured by TEAEs, Adverse Reactions (ARs), SAEs, Serious ARs (SARs) |
upto Day 28 |
|
Target Sample Size
|
Total Sample Size="40" Sample Size from India="40"
Final Enrollment numbers achieved (Total)= "41"
Final Enrollment numbers achieved (India)="41" |
Phase of Trial
|
Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
17/07/2020 |
Date of Study Completion (India) |
05/09/2020 |
Date of First Enrollment (Global) |
Date Missing |
Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
|
Years="0" Months="3" Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
Recruitment Status of Trial (India) |
Completed |
Publication Details
|
NIL |
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
|
This is an open label,
randomized, multicenter, two arm, parallel, comparative, controlled study. The study
will be conducted at approximately 10-12 centers in India, having qualified
Investigators. The study will be initiated only after the receipt of regulatory
and ethics committee (EC) approval.
After obtaining the informed consent, patients
will be screened via various assessments as mentioned in Schedule of Assessment
and eligible patients will be randomized in the study by allocating randomization
number. All randomized patients will receive either a daily dose of Nafamostat
Mesilate (0.1 mg/kg/hr for 24 hrs as continuous infusion) with standard of care
or only standard of care for 10 days. Patients will be hospitalized during the
treatment period till day of discharge. During the study, Specimen Collection,
Packaging and Transport of Nasopharyngeal swab & oropharyngeal swab will be
done. |