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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  
Name  Address 
NIL  NIL 
 
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)  
Status 
Approved/Obtained 
 
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. 
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