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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04045327
Other study ID # PMZ-2010/CT-3.1/2018
Secondary ID CTRI/2019/01/017
Status Completed
Phase Phase 3
First received
Last updated
Start date January 31, 2019
Est. completion date September 27, 2019

Study information

Verified date October 2019
Source Pharmazz, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.

Centhaquine (previously used names, centhaquin and PMZ-2010; International Non-proprietary Name (INN) recently approved by WHO is centhaquine) has been found to be an effective resuscitative agent in rat, rabbit and swine models of hemorrhagic shock, it decreased blood lactate, increased mean arterial pressure, cardiac output, and decreased mortality. An increase in cardiac output during resuscitation is mainly attributed to an increase in stroke volume. Centhaquine acts on the venous α2B-adrenergic receptors and enhances venous return to the heart, in addition, it produces arterial dilatation by acting on central α2A-adrenergic receptors to reduce sympathetic activity and systemic vascular resistance.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 105
Est. completion date September 27, 2019
Est. primary completion date September 23, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- 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. Blood Lactate level indicative of hypovolemic shock (>2.0 mmol/L).

Exclusion Criteria:

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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Normal saline + Standard Treatment
Normal Saline to be Used as Vehicle in the Phase-III Study to Assess Efficacy of PMZ-2010 as a Resuscitative Agent for Hypovolemic Shock
Centhaquine + Standard Treatment
Phase-III Study to Assess Efficacy of PMZ-2010 as a Resuscitative Agent for Hypovolemic Shock

Locations

Country Name City State
India Jawahar Lal Nehru Medical College & Attached Hospitals Ajmer
India Radiant Superspeciality Hospital Amravati
India People Tree Hospitals Bangalore
India KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre Belgaum
India Shri Guru Ram Rai Institute of Medical & Health Sciences Dehradun
India Department of Surgery, GSVM Medical College Kanpur
India Institute of Postgraduate Medical Education & Research and SSKM Hospital Kolkata
India King George's Medical University Lucknow
India Christian Medical College & Hospital Ludhiana
India Sidhu Hospital Pvt. Ltd. Ludhiana
India Department of General Medicine, JSS Hospital Mysuru
India Criticare Hospital & Research Institute Nagpur
India New Era Hospital & Research Institute Nagpur
India Rahate Surgical Hospital & ICU Nagpur
India Seven Star Hospital Nagpur Maha
India ACSR Government Medical College & Hospital Nellore
India Maulana Azad Medical College and associated Lok Nayak Hospital New Delhi
India Institute of Medical Sciences, Banaras Hindu University Varanasi

Sponsors (1)

Lead Sponsor Collaborator
Pharmazz, Inc.

Country where clinical trial is conducted

India, 

References & Publications (7)

Anil Gulati, Dinesh Jain, Nilesh Agrawal, Prashant Rahate, Soumen Das, Rajat Chowdhuri, Deba Dhibar, Madhav Prabhu, Sameer Haveri, Rohit Agarwal, Manish Lavhale. Clinical Phase II Results Of PMZ-2010 (centhaquin) As A Resuscitative Agent For Hypovolemic S

Gulati A, Lavhale MS, Garcia DJ, Havalad S. Centhaquin improves resuscitative effect of hypertonic saline in hemorrhaged rats. J Surg Res. 2012 Nov;178(1):415-23. doi: 10.1016/j.jss.2012.02.005. Epub 2012 Apr 2. — View Citation

Gulati A, Zhang Z, Murphy A, Lavhale MS. Efficacy of centhaquin as a small volume resuscitative agent in severely hemorrhaged rats. Am J Emerg Med. 2013 Sep;31(9):1315-21. doi: 10.1016/j.ajem.2013.05.032. Epub 2013 Jul 19. — View Citation

Kontouli Z, Staikou C, Iacovidou N, Mamais I, Kouskouni E, Papalois A, Papapanagiotou P, Gulati A, Chalkias A, Xanthos T. Resuscitation with centhaquin and 6% hydroxyethyl starch 130/0.4 improves survival in a swine model of hemorrhagic shock: a randomized experimental study. Eur J Trauma Emerg Surg. 2018 Jul 13. doi: 10.1007/s00068-018-0980-1. [Epub ahead of print] — View Citation

Lavhale MS, Havalad S, Gulati A. Resuscitative effect of centhaquin after hemorrhagic shock in rats. J Surg Res. 2013 Jan;179(1):115-24. doi: 10.1016/j.jss.2012.08.042. Epub 2012 Sep 2. — View Citation

Papalexopoulou K, Chalkias A, Pliatsika P, Papalois A, Papapanagiotou P, Papadopoulos G, Arnaoutoglou E, Petrou A, Gulati A, Xanthos T. Centhaquin Effects in a Swine Model of Ventricular Fibrillation: Centhaquin and Cardiac Arrest. Heart Lung Circ. 2017 Aug;26(8):856-863. doi: 10.1016/j.hlc.2016.11.008. Epub 2016 Dec 19. — View Citation

Papapanagiotou P, Xanthos T, Gulati A, Chalkias A, Papalois A, Kontouli Z, Alegakis A, Iacovidou N. Centhaquin improves survival in a swine model of hemorrhagic shock. J Surg Res. 2016 Jan;200(1):227-35. doi: 10.1016/j.jss.2015.06.056. Epub 2015 Jun 29. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Change in systolic and diastolic blood pressure Change in systolic and diastolic blood pressure - Mean through 48 hours 48 hours
Primary Change in blood lactate level Change in blood lactate level - Mean through 48 hours 48 hours
Primary Change in base-deficit Change in Base-deficit - Mean through 48 hours 48 hours
Secondary Total Urine Output Total volume of urine output - Mean through 48 hours 48 hours
Secondary Vasopressor(s) infused Amount of total vasopressor(s) infused - Mean through 48 hours 48 hours
Secondary Volume of fluid administered Total volume of fluid administered - Mean through 48 hours 48 hours
Secondary Doses of study drug Number of doses of study drug administered in first 48 hours post randomization 48 hours
Secondary Incidence of mortality Proportion of patients with all-cause mortality at 48 hours and 28 days 28 days
Secondary Stay in hospital, in ICU and/or on Ventilator Days in hospital, in ICU and/or on Ventilator - Mean through 28 days 28 days
Secondary Change in Multiple Organ Dysfunction Syndrome Score Change in Multiple Organ Dysfunction Syndrome Score (MODS) - Mean through 28 days. MODS is a 5 grade scale from 0 to 4, where 0 is the best and 4 is the worst outcome. 28 days
Secondary Change in Acute Respiratory Distress Syndrome Change in Acute Respiratory Distress Syndrome (ARDS) - Mean through 28 days. ARDS will be determined using Murray Score for Acute Lung Injury which is based upon radiological findings, oxygenation status, ventilation status of the patient. A lower score of 0 is the best and about 2.5 is the worst outcome. 28 days
Secondary Change in Glasgow coma score Change in Glasgow coma score (GCS) - Mean through 28 days. GCS is a 15 point scale to assess the level of consciousness of patients where less than 3 is comatose state and 15 is fully awake. 28 days
Secondary Incidence of adverse events Proportion of patients with drug related adverse events during 28 days 28 days
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