CTRI/2019/01/017196 [Registered on: 22/01/2019] Trial Registered Prospectively
Last Modified On:
02/02/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
Effect of PMZ-2010 in Hypovolemic Shock patients.
Scientific Title of Study
A Prospective, Multi-Centric, Randomized, Double-Blind, Parallel, Phase-III Study to Assess
Efficacy of PMZ-2010 as a Resuscitative Agent for Hypovolemic Shock to be Used as an Adjuvant to Standard Shock Treatment.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
PMZ-2010/CT-3.1/2018, Version 1.0/16 July 2018
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
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
Ethics Committe, Room No 125, GSVM Medical College, Kanpur-208002, U.P.
Approved
Ethics Committee New Era Hospital, Central Avenue Road, Near Telephone Exchange Chowk, Queta Colony, Near Jalaram Mandir Nagpur-440008.
Approved
Ethics Committee, Criticare Hospital & Research Institute, 4th Floor, Dhanshree Complex, Near Hotel Hardeo, Sitabuldi, Nagpur-440012, Maharashtra, India
Approved
Ethics Committee, Rahate Surgical Hospital, Conference Room, 4th Floor, Near Telephone Exchange Square, 517-Juni Mangalwari, Central Avenue, Nagpur 440008, Maharashtra, India
Approved
Ethics Committee, Rahate Surgical Hospital, Conference Room, 4th Floor, Near Telephone Exchange Square-517 Juni Mangalwadi, Central Avenue, Nagpur-440008
Approved
Institutional Ethics Committee C/o Principal Office, Christian Medical College & Hospital, Brown Road, Ludhiana- 141008, Punjab, India
Approved
Institutional Ethics Committee, AC Subba Reddy Government Medical College & Hospital,Opp. AC Stadium, Dargamitta, GT Road, Nellore-524007, Andhra Pradesh, India
Approved
Institutional Ethics Committee, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India
Approved
Institutional Ethics Committee, Jawahar Lal Nehru Medical College, Kala Bagh, Ajmer-305001, Rajasthan, India
Approved
Institutional Ethics Committee, Jawahar Lal Nehru Medical College. Kala Bagh, Ajmer-305001, Rajasthan.
Institutional Ethics Committee, KLE’s University, JN Medical College, Nehru Nagar- Belagavi 590010, Karnataka, India
Approved
Institutional Ethics Committee, Maulana Azad Medical College,3rd Floor, Room No .-306B, Bahadur Shah Zafar Marg, Maulana Azad Medical College Campus, Balmiki Basti, New Delhi-110002
Approved
Institutional Ethics Committee, Nirmal Hospital, Opp. Gate No. -3, M.L.B. Medical College, Jhansi - 284128, Uttar Pradesh, India
Approved
Institutional Ethics Committee, Office of Research Cell, Administrative Block, King George’s Medical University, Lucknow 226003 Uttar Pradesh, India
Approved
Institutional Ethics Committee, Shri Guru Ram Rai Institute of Medical & Health Sciences, Administrative Building, Patel Nagar, Dehradun - 248001, Uttarakhand, India
Approved
Institutional Review Board of Sidhu Educational Research Institute & Hospital, G.T. Road, Doraha, Dist. Ludhiana-141421
Approved
IPGME&R Research Oversight Committee, Institute of Post Graduate Medical Education & Research, Office of Dean, College Building, 5th Floor, 244, Acharya JC Bose Road, Kolkata 700020, India
Approved
People Tree Hospitals Ethics Committee, No-2, Tumkur Road, Next to Metro Station, Goraguntepalya, Yeshwanthpur, Bangalore-560022, Karnataka, India
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 ≤ 90 mmHg at presentation and continue to receive standard Shock Treatment.dose of PMZ-2010 (0.01 mg/kg) will be administered as an intravenous (IV) 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 or equal to 90 mmHg but not before 4 hours of previous dose and total doses per day (in 24 hours) 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 hours 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 intravenous (IV) infusion over 1 hour in 100 mL of normal saline post randomization. Second dose of Normal Saline will be administered if SBP falls below or remains below or equal to 90 mmHg but not before 4 hours of previous dose and total doses per day (in 24 hours) will not exceed 3 doses. Normal Saline administration if needed will continue for two days post randomization. Minimum 1 dose or maximum 6 doses of Normal Saline will be administered within first 48 hours post randomization. Conditions of administration will remain same as for PMZ-2010 group.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
90.00 Year(s)
Gender
Both
Details
1. Adult males or females aged 18 years or older.
2. Patients with Hypovolemic shock admitted to the emergency room or ICU with systolic blood pressure ≤ 90 mmHg at presentation and continue to receive standard shock treatment (endotracheal intubation; fluid resuscitation and vasopressors). Standard of care to be provided to the patients shall be the one used in the particular hospital setup.
3. Blood Lactate level indicative of hypovolemic shock.
ExclusionCriteria
Details
1. Development of any other terminal illness not associated with Hypovolemic shock during the 28-day observation period.
2. Patient with altered consciousness not due to Hypovolemic shock.
3. Known pregnancy.
4. Cardiopulmonary resuscitation (CPR) before randomization.
5. Presence of a do not resuscitate order.
6. Patient is participating in another interventional study.
7. Patients with systemic diseases which were already present before having trauma, such as: cancer, chronic renal failure, liver failure, decompensated heart failure or AIDS.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
1. Change in systolic and diastolic blood pressure, Mean through 48 hours.
2. Change in blood lactate, Mean through 48 hours.
3. Change in Base-deficit, Mean through 48 hours.
Through first 48 hours.
Secondary Outcome
Outcome
TimePoints
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
Total Urine Output
First 48 hours
Amount of total vasopressor(s) infused
First 48 hours
Total volume of fluid administered inclusive of crystalloids, blood products, mannitol and other colloids.
First 48 hours
Proportion of patients with all-cause mortality
At 48 hours and 28 days
Number of doses of PMZ-2010 administered post randomization
First 48 hours
Change in Multiple Organ Dysfunction Syndrome Score (MODS)
28 days
Change in Acute Respiratory Distress Syndrome (ARDS) Free Survival
28 days
Change in Glasgow coma score
28 days
Proportion of patients with adverse events (AEs) and serious adverse events (SAEs).
28 days
Target Sample Size
Total Sample Size="105" Sample Size from India="105" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="105"
(1) Clinical Phase II Results of PMZ-2010 as a Resuscitative Agent for Hypovolemic Shock, Critical Care Medicine. 2018; 47(1). (2) PMZ-2010 as a Novel Resuscitative Agent for Hypovolemic Shock. Circulation. 2018; 138: A13092. (3) Human Pharmacokinetics of Centhaquin Citrate, a Novel Resuscitative Agent. Circulation. 2016; 134:A16607. (4) Safety and Efficacy of Centhaquin as a Novel Resuscitative Agent for Hypovolemic Shock. Circulation. 2015; 132:A17521.
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
This is a prospective, multi-centric, randomized, double-blind, parallel, controlled phase-III efficacy clinical study of PMZ-2010 therapy in patients with Hypovolemic shock with systolic arterial blood pressure ≤ 90 mmHg at presentation and continue to receive standard Shock Treatment. The enrolment period of the study will be approximately 09 months and total duration of the study will be approximately 15 months. For an individual patient, 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 + 7). At visit 1, approximately 105 patients will be randomized 2:1 into 2 treatment groups after meeting the eligibility criteria. Total 70 patients will be enrolled in PMZ-2010 group (Group 1) and in Normal Saline group (Group 2) total 35 patients will be enrolled.
• 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 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 at presentation and continue to receive standard Shock Treatment. In PMZ-2010 group, dose of PMZ-2010 (0.01 mg/kg) will be administered as an intravenous (IV) 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 or equal to 90 mmHg but not before 4 hours of previous dose and total doses per day (in 24 hours) 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 hours. post randomization. In Control group, single dose of equal volume of Normal Saline will be administered as intravenous (IV) infusion over 1 hour in 100 mL of normal saline post randomization. Condition of administration will remain same as for PMZ-2010 group. Each patient will be monitored closely throughout his/her hospitalization and will be followed until discharge from randomization. Each patient will be assessed for efficacy parameters over 28 days from randomization to a clinic visit.