Efficacy of PMZ-2010 (Centhaquine) a Resuscitative Agent for Hypovolemic Shock

October 3, 2019 updated by: Pharmazz, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

105

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
      • Ajmer, India, 305001
        • Jawahar Lal Nehru Medical College & Attached Hospitals
      • Amravati, India, 444606
        • Radiant Superspeciality Hospital
      • Bangalore, India, 560022
        • People Tree Hospitals
      • Belgaum, India, 590010
        • KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
      • Dehradun, India, 248001
        • Shri Guru Ram Rai Institute of Medical & Health Sciences
      • Kanpur, India, 208002
        • Department of Surgery, GSVM Medical College
      • Kolkata, India, 700020
        • Institute of Postgraduate Medical Education & Research and SSKM Hospital
      • Lucknow, India, 226003
        • King George's Medical University
      • Ludhiana, India, 141008
        • Christian Medical College & Hospital
      • Ludhiana, India, 141421
        • Sidhu Hospital Pvt. Ltd.
      • Mysuru, India, 570004
        • Department of General Medicine, JSS Hospital
      • Nagpur, India, 440008
        • New Era Hospital & Research Institute
      • Nagpur, India, 440008
        • Rahate Surgical Hospital & ICU
      • Nagpur, India, 440012
        • Criticare Hospital & Research Institute
      • Nellore, India, 524007
        • ACSR Government Medical College & Hospital
      • New Delhi, India, 110002
        • Maulana Azad Medical College and Associated Lok Nayak Hospital
      • Varanasi, India, 221005
        • Institute of Medical Sciences, Banaras Hindu University
    • Maha
      • Nagpur, Maha, India
        • Seven Star Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Normal Saline
Hypovolemic shock patients will be provided the standard of care. Following randomization 100 ml (equal volume to experimental arm) of normal saline will be administered intravenously over 1 hour.
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
Other Names:
  • Vehicle
Experimental: PMZ-2010 (centhaquine)
Hypovolemic shock patients will be provided the standard of care. Following randomization PMZ-2010 (0.01 mg/kg) will be administered intravenously over 1 hour in 100 mL of normal saline.
Drug: Centhaquine + Standard Treatment
Phase-III Study to Assess Efficacy of PMZ-2010 as a Resuscitative Agent for Hypovolemic Shock
Other Names:
  • PMZ-2010

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in systolic and diastolic blood pressure
Time Frame: 48 hours
Change in systolic and diastolic blood pressure - Mean through 48 hours
48 hours
Change in blood lactate level
Time Frame: 48 hours
Change in blood lactate level - Mean through 48 hours
48 hours
Change in base-deficit
Time Frame: 48 hours
Change in Base-deficit - Mean through 48 hours
48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Urine Output
Time Frame: 48 hours
Total volume of urine output - Mean through 48 hours
48 hours
Vasopressor(s) infused
Time Frame: 48 hours
Amount of total vasopressor(s) infused - Mean through 48 hours
48 hours
Volume of fluid administered
Time Frame: 48 hours
Total volume of fluid administered - Mean through 48 hours
48 hours
Doses of study drug
Time Frame: 48 hours
Number of doses of study drug administered in first 48 hours post randomization
48 hours
Incidence of mortality
Time Frame: 28 days
Proportion of patients with all-cause mortality at 48 hours and 28 days
28 days
Stay in hospital, in ICU and/or on Ventilator
Time Frame: 28 days
Days in hospital, in ICU and/or on Ventilator - Mean through 28 days
28 days
Change in Multiple Organ Dysfunction Syndrome Score
Time Frame: 28 days
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
Change in Acute Respiratory Distress Syndrome
Time Frame: 28 days
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
Change in Glasgow coma score
Time Frame: 28 days
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
Incidence of adverse events
Time Frame: 28 days
Proportion of patients with drug related adverse events during 28 days
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pharmazz, Inc.

Investigators

  • Study Chair: Anil Gulati, MD, PhD, Pharmazz, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2019

Primary Completion (Actual)

September 23, 2019

Study Completion (Actual)

September 27, 2019

Study Registration Dates

First Submitted

July 31, 2019

First Submitted That Met QC Criteria

August 2, 2019

First Posted (Actual)

August 5, 2019

Study Record Updates

Last Update Posted (Actual)

October 4, 2019

Last Update Submitted That Met QC Criteria

October 3, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PMZ-2010/CT-3.1/2018
  • CTRI/2019/01/017196 (Registry Identifier: Clinical Trials Registry - India)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Plan to publish the findings after completion of the study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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