| CTRI Number |
CTRI/2016/06/007046 [Registered on: 29/06/2016] Trial Registered Prospectively |
| Last Modified On: |
21/06/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
PMS |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A Phase IV study to evaluate safety and efficacy of Intravenous Ulinastatin versus Placebo administered along with standard supportive care |
|
Scientific Title of Study
|
Prospective, Multi-centric, Double-blind, Comparative, Clinical Study To Compare The Efficacy And Safety of Intravenous Ulinastatin versus Placebo Adjunct To Standard Supportive Care In Subjects With Severe Sepsis, A Phase IV study. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| LU-03-13 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Mangesh Kamle |
| Designation |
Manager Medical Services |
| Affiliation |
Lupin Limited |
| Address |
Laxmi Towers C Wing 5th Floor Bandra Kurla Complex Mumbai
Mumbai
MAHARASHTRA
400051
India |
| Phone |
02266402954 |
| Fax |
02266402222 |
| Email |
mangeshkamle@lupin.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Mangesh Kamle |
| Designation |
Manager Medical Services |
| Affiliation |
Lupin Limited |
| Address |
Laxmi Towers C Wing 5th Floor Bandra Kurla Complex Mumbai
The Dangs
MAHARASHTRA
400051
India |
| Phone |
02266402954 |
| Fax |
02266402222 |
| Email |
mangeshkamle@lupin.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Chirag Shah |
| Designation |
Head - Clinical Trials |
| Affiliation |
Cliantha Research Limited |
| Address |
Cliantha Research Limited, Garden View Corporate House, Sindhu Bhavan Road, Bodakdev, Ahmedabad
Ahmadabad
GUJARAT
3800054
India |
| Phone |
07966219531 |
| Fax |
07966219549 |
| Email |
cshah@cliantha.in |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Lupin Limited |
| Address |
159, CST Road, Kalina, Santacruz (East), Mumbai |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Rajat Choudhuri |
Institute of Post Graduate Medical Education And Research |
Institute of Post Graduate Medical Education And Research 244 A.J.C Bose Road, Kolkata - 700 020
Kolkata
WEST BENGAL |
09830723174
rajat.choudhuri@gmail.com |
| Dr Kotiwale Veerappa Annasaheb |
KLES, Prabhakar Kore hospital & Medical research centre |
KLES, Prabhakar Kore hospital & Medical research centre, Nehru Nagar, Belgaum – 590010, Karnataka, India
Belgaum
KARNATAKA |
08312437835
nov10kothiwale@yahoo.co.in |
| Dr K Sunil Naik |
Rajiv Gandhi Institute of Medical Sciences & RIMS Govt |
Dept. of Medicine, Rajiv Gandhi Institute of Medical Sciences & RIMS Govt., General Hospital, Srikakulam - 532001, Andhra Pradesh, India
Srikakulam
ANDHRA PRADESH |
08942279033
rimsresearch@gmail.com |
| Dr Atul Gogia |
Sir Gangaram Hospital |
Sir Gangaram Hospital, Sir Gangaram Hospital Marg, Rajinder Nagar, New Delhi – 110060, India
New Delhi
DELHI |
09891003450
atulgogia@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Ethics Committee, KLE, KLES, Prabhakar Kore hospital & Medical research centre, Nehru Nagar, Belgaum – 590010, Karnataka, India |
Submittted/Under Review |
| Ethics Committee, Sir Ganga Ram Hospital, Sir Gangaram Hospital Marg, Rajinder Nagar, New Delhi – 110060, India |
Submittted/Under Review |
| Institutional Ethics Committee, Rajiv Gandhi Institute of Medical Sciences & RIMS Govt., General Hospital, Srikakulam - 532001, Andhra Pradesh, India |
Approved |
| IPGME & R Research Oversight Committee, Office of the Dean, College Building, 5th Floor, Institute of Post Graduate Medical Education & Research, 244 Acharya J.C Bose Road, Kolkata - 700020, West Bengal, India |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Severe Sepsis, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo |
Placebo will be administered (dissolved in 100 ml of 0.9% saline or 5 % dextrose) given IV over one hour every 12 hours along with standard supportive care for 7 days. |
| Intervention |
Ulinastatin |
Ulinastatin will be administered in a dose of 200,000 IU (dissolved in 100 ml of 0.9% saline or 5 % dextrose) given IV over one hour every 12 hours along with standard supportive care for 7 days. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Males and females of age ≥18 years and ≤65 years.
2. Infection: Proved or suspected infection in at least one site:
• lung
• abdomen
• genitourinary tract
• other (blood, skin and soft tissue, central nervous system, bones and joints, cardiac system, catheter related infection)
3. Modified SIRS Criteria: Patient has to meet at least three of the following four criteria:
• A core temperature of ≥ 38º C (100.4º F) or ≤ 36º C (96.8º F).
• Heart rate of ≥90 beats/min, except in patients with a medical condition known to increase the heart rate or those receiving treatment that would prevent tachycardia.
• Respiratory rate ≥20 breaths/min or PaCO2 of ≤32 mmHg or the use of mechanical ventilation for an acute respiratory process.
• A white cell count of ≥12,000/mm3 or ≤4,000/mm3 or a differential count showing >10% immature neutrophils.
4. Criteria for Dysfunctional Organs or Systems: Patient has to meet at least one of the following six criteria:
• For cardiovascular system dysfunction, the arterial systolic blood pressure (SBP) has to be ≤90 mmHg or the mean arterial pressure ≤70 mmHg for at least 1 hour despite adequate fluid resuscitation, adequate intravascular volume status or the use of vasopressors in an attempt to maintain a SBP of ≥90 mmHg or a mean arterial pressure of ≥70 mmHg.
• For kidney dysfunction, urine output has to be <0.5 ml/kg of body weight/ hour for 1 hour, despite adequate fluid resuscitation.
• For respiratory dysfunction, the ratio of partial pressure of oxygen in arterial blood (PaO2) to fraction of inspired oxygen (FiO2) has to be ≤250 in the presence of other dysfunctional organs or systems or ≤200 if the lung is the only dysfunctional organ.
• For hematologic dysfunction, the platelet count has to be <80,000/mm3 or to have decreased by 50% in the 3 days preceding enrolment.
• In the case of unexplained metabolic acidosis, the pH has to be ≤7.30 or the base deficit has to be ≥ 5.0 mmol/L in association with a plasma lactate level that is >1.5 times the upper limit of the normal (ULN) value for the reporting laboratory.
• For hepatic dysfunction, total bilirubin >1.5 mg/dL and/or Alanine Transaminase (ALT)/Aspartate Transaminase (AST) >3 times the upper limit of the normal value for the reporting laboratory.
5. Written informed consent by subject or LAR.
|
|
| ExclusionCriteria |
| Details |
Subjects who meet any of the following criteria will be excluded from the study:
1. Patient with platelet count <30,000/mm3.
2. Conditions that increase the risk of bleeding.
3. Patient’s family, physician, or both not in favour of aggressive treatment of patient or presence of an advanced directive to withhold life-sustaining treatment.
4. Patient not expected to survive 28 days because of uncorrectable medical condition, such as poorly controlled neoplasm or other end stage disease.
5. History of bone marrow, lung, liver, pancreas or small-bowel transplantation.
6. Patients with incurable malignancies with documented metastases.
7. Chronic renal failure requiring haemodialysis or peritoneal dialysis.
8. Known or suspected portosystemic hypertension, chronic jaundice, cirrhosis or chronic ascites.
9. Deep seated fungal infection or active tuberculosis.
10. History of chronic hypercarbia, respiratory failure in past 6 months or use of home oxygen in the setting of severe chronic respiratory disease.
11. Neuromuscular disorders that impact breathing/spontaneous ventilation.
12. Quadriplegia.
13. Cardiac arrest in the past 30 days.
14. New York Heart Association functional Class III and IV due to heart failure or any disorder.
15. Burns over >30% of body surface area.
16. Allergy for Ulinastatin.
17. Pregnant or lactating females or females of child bearing potential who are not willing for using adequate methods of contraception.
18. Participation in another clinical study within 30 days prior to the study. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Percentage of subjects with reduction in mortality rate |
Day 28 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1.To evaluate the average length of hospital stay (days)
2.Percentage of subjects achieving subsidence of sepsis
3.Percentage of subjects achieving prevention of new onset organ failure
4.To assess the duration of ventilation, if any
5.Assessment of safety of Ulinastatin in terms of incidence of treatment emergent adverse events (TEAE). |
Day 28 or discharge day from Hospital, whichever is earlier |
|
|
Target Sample Size
|
Total Sample Size="200"
Sample Size from India="200"
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 4 |
|
Date of First Enrollment (India)
|
20/07/2016 |
| 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) |
Not Yet Recruiting |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Studies in patients with sepsis have shown that
there is a decrease in serum levels of Ulinastatin, with lowest levels being
found in patients with severe sepsis and septic shock. Previous
studies have shown that Ulinastatin administration to patients with SIRS
reduces the levels of pro-inflammatory cytokines such as polymorphonuclear
leukocyte elastase, tumor necrosis factor-alpha and Interleukin 6 and
serum C‑reactive protein and increase in the levels of anti‑inflammatory
cytokine Interleukin-10. In few studies, Ulinastatin has also shown reduction
in the mortality, confirming the benefit of its addition to patients with
sepsis, severe sepsis and shock.
Primary Objective of the study is to evaluate the
28-day mortality
|