| CTRI Number |
CTRI/2017/03/008184 [Registered on: 22/03/2017] Trial Registered Prospectively |
| Last Modified On: |
20/12/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Study the safety and efficacy of PMZ-2010 in patients with shock due to blood loss. |
|
Scientific Title of Study
|
A Prospective, Multi-centric, Randomized, Double-blind, Parallel, Saline Controlled Phase II Safety and Efficacy study of PMZ-2010 as a resuscitative agent for Hypovolemic Shock due
to excessive blood loss to be used along with standard shock treatment. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| PMZ-02, Version 2.0/10 March 2016 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Atul Mishra |
| Designation |
Principal Investigator |
| Affiliation |
Dayanand Medical College and Hospital |
| Address |
Department of Surgery, First floor, Civil Lines, Tagore Nagar, Near Rose Garden
Ludhiana
PUNJAB
141001
India |
| Phone |
9814163473 |
| Fax |
|
| Email |
atul1970@hotmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Manish S Lavhale |
| Designation |
Associate Director |
| Affiliation |
Pharmazz India Private Limited |
| Address |
H-6, Site-C, Surajpur Industrial Area, Greater Noida, Uttar Pradesh India
Gautam Buddha Nagar
UTTAR PRADESH
201307
India |
| Phone |
9873847397 |
| Fax |
|
| Email |
manish.lavhale@pharmazz.com |
|
Details of Contact Person
Public Query
|
| Name |
Mr Sunil Gulati |
| Designation |
Chief Operating Officer |
| Affiliation |
Pharmazz India Private Limited |
| Address |
H-6, Site-C, Surajpur Industrial Area, Greater Noida, Uttar Pradesh India
Gautam Buddha Nagar
UTTAR PRADESH
201307
India |
| Phone |
9811406340 |
| Fax |
|
| Email |
sunil.gulati@pharmazz.com |
|
|
Source of Monetary or Material Support
|
| Pharmazz India Private Limited, H-6, Site-C, Surajpur Industrial Area, Greater Noida UP 201307 |
|
|
Primary Sponsor
|
| Name |
Pharmazz India Private Limited |
| Address |
H-6, Site-C, Surajpur Industrial Area,
Greater Noida – 201307, Uttar Pradesh, 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 Rajesh Kumar Pande |
BLK Super Speciality Hospital |
Department of Critical Care and Emergency Medicine, 5 Pusa Road, New Delhi 110005
New Delhi
DELHI |
9810536268
rajeshmaitree2000@gmail.com |
| Dr Atul Mishra |
Dayanand Medical College and Hospital |
Department of Surgery, First Floor, Civil Lines, Tagore Nagar, Near Rose Garden, Ludhiana 141001
Ludhiana
PUNJAB |
9814163473
atul1970@hotmail.com |
| Dr Soumen Das |
Institute of Post Graduate Medical Education and Research (IPGME&R) and SSKM Hospital |
Department of Surgery, 244 A.J.C. Bose Road, Kolkata 700020
Kolkata
WEST BENGAL |
9830282494
soumendoc.das@gmail.com |
| Dr Madhav Prabhu |
KLE’s Dr. Prabhakar Kore Hospital and Medical Research Centre |
Department of Medicine,
Nehru Nagar, Belgaum 590010
Belgaum
KARNATAKA |
9341101268
maddy2380@gmail.com |
| Dr Nilesh Agrawal |
NewEra Hpspital |
Department of Neurology, Central Avenue Road, Near Telephone Exchange Chowk, Queta Colony, Near Jalaram Mandir 440008
Nagpur
MAHARASHTRA |
8888667808
anileshr@gmail.com |
| Dr Harendra Thakker |
Shalby Hospitals |
Department of Pulmonology and Critical Care Medicine,
Opposite Karnavati Club,
S.G.Highway, Ahmedabad 380015
Ahmadabad
GUJARAT |
9825060436
harendra.thakker@shalby.org |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 12 |
| Name of Committee |
Approval Status |
| Dr B.L Kapur Memorial Hospital Ethics Committee Dr B L Kapur Memorial Hospital Pusha Road New Delhi |
Approved |
| Drug Trial Ethics Committee Dayanand Medical College and Hospital Ludhiana Punjab |
Approved |
| Ethics Committee of the Prakhar Hospital 8/219 Arya Nagar Kanpur Uttar Pradesh |
Approved |
| Ethics Committee Rahate Surgical Hospital Near Telephone Exchange Square 517-Juni Mangalwari Centreal Avenue Nagpur-440008 |
Approved |
| Ethics Committee, Krishna Shalby Hospital, Ahmedabad |
Approved |
| Institutional Ethics Committee Heritage Institute of Medical Sciences,Varanasi, UP-221311 |
Approved |
| Institutional Ethics Committee GCS Medical College Hospital and research Center Naroda Road Ahmedabad |
Approved |
| Institutional Ethics Committee Postgraduate Institute of Medical Education and Research, Chandigarh |
Approved |
| Institutional Ethics Committee, KLE University, Belgaum |
Approved |
| IPGME&R Research Oversight Committee Kolkata |
Approved |
| NewEra Hospital Ethics Committee, NewEra Hospital, Nagpur |
Approved |
| Oriana Hospital Ethics Committee Plot no 678 Ravindrapuri Bhelupur Varanasi-221005 UP |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Hypovolemic shock due to blood loss, (1) ICD-10 Condition: T794||Traumatic shock, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Lyophilized Centhaquin Injection
(PMZ-2010)
|
PMZ-2010 (Dose: 0.01 mg/kg) + Standard of care: PMZ-2010 will be administered intravenously after randomization to hypovolemic shock patients with systolic arterial blood pressure (SBP) below 90 mmHg even after 10 min of standard shock treatment. Dose of PMZ-2010 (0.01 mg/kg) will be administered as an intravenous infusion over 1 hour in 100 mL of normal saline. Second dose of PMZ-2010 will be administered if SBP falls below or remains below 90 mmHg but not before 4 hours of previous dose and total doses per day will not exceed 3 doses. PMZ-2010 administration if needed will continue for two days post randomization. Minimum 1 dose or maximum 6 doses of PMZ-2010 will be administered within first 48 hrs post randomization. |
| Comparator Agent |
Normal Saline |
Normal Saline (Dose: Equal volume) + Standard of care: In Control group, doses of equal volume of Normal Saline will be administered as an IV infusion over 1 hour in 100 mL normal saline post randomization. Second dose of Normal Saline will be administered if SBP falls below or remains below 90 mmHg but not before 4 hours of previous dose and total doses per day will not exceed more than 3 doses. Normal Saline administration if needed will continue for two days post randomization. Minimum one or maximum 6 doses of Normal Saline will be administered within first 48 hrs post randomization. Condition of administration will remain same as for PMZ-2010 group. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
a. Adult males or females aged 18-60 years.
b.Patients with Hypovolemic shock due to blood loss admitted to the emergency room or ICU with systolic blood pressure <90 mmHg even after 10 min of standard shock treatment (endotracheal intubation; fluid resuscitation and vasopressors). Standard care to be provided to the patients shall be the one used in the particular hospital setup.
c.Body weight 45 kg – 85 kg
d. Estimated time from injury to randomization <4 hours
e. Subject is <4 hours from time of Hypovolemic shock onset when the first dose of PMZ-2010 therapy is administered. Time of onset is when symptoms began; Reasonable expectation of availability to receive the full PMZ-2010 course of therapy, and to be available for subsequent follow-up visits
f. Female subject is either:
Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)
or,
If of childbearing potential, agrees to use any of the following effective separate forms of contraception throughout the study, up to and including the follow-up visits: Condoms, sponge, foams, jellies, diaphragm or intrauterine device, or A vasectomised partner OR abstinence |
|
| ExclusionCriteria |
| Details |
a. Terminal illness
b. Development of any other terminal illness not associated with Hypovolemic shock during the 28 day observation period.
c. Evidence of severe blunt or penetrating head injury with a Glasgow Coma Scale (GCS) ≤ 8
d. Type of injury is not known
e. Inability to obtain intravenous access
f.Known pregnancy
g. Cardiopulmonary resuscitation (CPR) before randomization
h. Presence of a do not resuscitate order
i. Patient taking beta adrenergic antagonists
j. Untreated tension pneumothorax
k. Untreated cardiac tamponade
l.Bilateral absent pupillary light reflex (both pupils fixed and dilated)
m. Patient is participating in another interventional study
n.Presence of systemic diseases (cancer, chronic renal failure, liver failure, decompensated heart failure or AIDS)
o.Patients with triad of coagulopathy, acidosis and hypothermia that requires immediate blood transfusion |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Proportion of subjects with adverse events (AEs) and serious adverse events (SAEs) |
28 Days |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Proportion of subjects discharged from hospital.
|
Through Day 28 and alive at the Day 28 Follow up visit. |
| Days in hospital, in ICU and/or on Ventilator. |
The number of days beginning with the day of the episode counted as “Day 0†through Day 28 during which the patient is being cared in the hospital, or on ventilator or in ICU. |
| Proportion of subjects with all cause mortality. |
At 48 hours and 28 days. |
| Total fluids requirement and total volume of fluid administered (inclusive of crystalloids, blood products, 3% saline, mannitol and other colloids). |
First 48 hours. |
| Total Blood product requirements and total amount of blood products required (packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets, cryoprecipitate. |
First 48 hours. |
| Amount and duration of total vasopressor(s) infused. |
First 48 hours. |
| Number of doses of PMZ-2010 administered. |
First 48 hours. |
| Change in Hemodynamic variables. |
First 48 hours. |
| Change in blood hematocrit and hemoglobin. |
First 48 hours. |
| Change in blood lactate. |
First 48 hours. |
| Change in Base-deficit. |
First 48 hours. |
| Change in Coagulation parameters (Platelets, Prothrombin time, INR and fibrinogen values). |
First 48 hours. |
| Change in Multiple Organ Dysfunction Score (MODS). |
28 days |
| Change in Adult Respiratory Distress Syndrome (ARDS) Free Survival. |
28 days |
| Change in Glasgow outcome score. |
28 days |
|
|
Target Sample Size
|
Total Sample Size="50"
Sample Size from India="50"
Final Enrollment numbers achieved (Total)= "50"
Final Enrollment numbers achieved (India)="50" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
27/03/2017 |
| Date of Study Completion (India) |
21/10/2018 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="9"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
Gulati A, Goyal AO, Lavhale MS, Gulati S and M. S (2016) Human Pharmacokinetics of Centhaquin Citrate, a Novel Resuscitative Agent. Circulation 134:A16607.
Goyal AO, Lavhale MS and Gulati A (2015) Safety and Efficacy of Centhaquin as a Novel Resuscitative Agent for Hypovolemic Shock. Circulation 132:A17521.
Papapanagiotou P, Xanthos T, Gulati A, Chalkias A, Papalois A, Kontouli Z, Alegakis A and Iacovidou N (2015) Centhaquin improves survival in a swine model of hemorrhagic shock. J Surg Res 200(1):227-235.
Gulati A, Zhang Z, Murphy A and Lavhale MS (2013) Efficacy of centhaquin as a small volume resuscitative agent in severely hemorrhaged rats. Am J Emerg Med 31:1315-1321.
Lavhale MS, Havalad S and Gulati A (2013) Resuscitative effect of centhaquin after hemorrhagic shock in rats. J Surg Res 179:115-124. |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
This is a prospective, multicentric, randomized, double- blind, parallel, saline controlled Phase II Safety and Efficacy clinical study of PMZ-2010 therapy in subjects with Hypovolemic shock due to blood loss with systolic arterial blood pressure < 90 mmHg after 10 min of standard Shock Treatment. A total of 50 subjects (25 in each arm) will be enrolled in the study. The enrolment period of the study will be approximately 03 months and total duration of the study will be approximately 09 months. For an individual subject, duration of the study will be 1 month (28 days), including 2 study visits: visit 1/Day 1 (screening/randomization/baseline/treatment visit), and visit 2/End of Study (Day 28 + 5). At visit 1, approximately 50 subjects will be randomized 1:1 into 2 treatment groups after meeting the eligibility criteria: Group 1: PMZ-2010 (Dose: 0.01 mg/kg) + Standard of care Group 2: Normal Saline (Dose: Equal volume) + Standard of care In both treatment groups, patients will be provided the best standard of care. PMZ-2010 or Normal Saline will be administered intravenously after randomization to hypovolemic shock patients with systolic arterial blood pressure < 90 mmHg even after 10 min of standard shock treatment. In PMZ-2010 group, dose of PMZ-2010 (0.01 mg/kg) will be administered as an intravenous infusion over 1 hour in 100 mL of normal saline. Second dose of PMZ-2010 will be administered if SBP falls below or remains below 90 mmHg but not before 4 hours of previous dose and total doses per day will not exceed 3 doses. PMZ-2010 administration if needed will continue for two days post randomization. Minimum 1 dose or maximum 6 doses of PMZ-2010 will be administered within first 48 hrs post randomization. In Control group, single dose of equal volume of Normal Saline will be administered as intravenous infusion over 1 hour in 100 mL of normal saline post randomization. Condition of administration will remain same as for PMZ-2010 group. Each subject will be monitored closely throughout his/her hospitalization and will be followed until discharge from randomization. Each subject will be assessed for efficacy and safety parameters over 28 days from randomization to a clinic visit. |