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

August 13, 2019 updated by: Pharmazz, Inc.

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 to be Used Along With Standard Shock Treatment.

This is a prospective, multi-centric, randomized, double-blind, parallel, controlled phase-II efficacy clinical study of PMZ-2010 therapy in patients with hypovolemic shock.

Centhaquine is highly safe and well tolerated. Toxicological studies showed high safety margin in preclinical studies. Its safety and tolerability has been demonstrated in a human phase I study in 25 subjects (CTRI/2014/06/004647; NCT02408731).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Unlike presently used vasopressors, centhaquine increased mean arterial pressure by increasing stroke volume and cardiac output, and it decreased systemic vascular resistance. The most common adverse effects of vasopressors as a class include arrhythmias, fluid extravasation, and ischemia. Centhaquine does NOT act on beta-adrenergic receptors, and therefore the risk of arrhythmias is mitigated. It is NOT a vasopressor; however, it increases blood pressure and cardiac output by augmenting venous blood return to the heart and enhanced tissue perfusion by arterial dilatation. Enhancing tissue perfusion is a significant advantage over existing vasopressors.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

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
      • Belgaum, India, 590010
        • KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
      • Chandigarh, India, 160012
        • Post Graduate Institute of Medical education and Research
      • Kolkata, India, 700020
        • Institute of Postgraduate Medical Education & Research and SSKM Hospital
      • Ludhiana, India, 141001
        • Dayanand Medical College & Hospital
      • Nagpur, India, 440008
        • New Era Hospital & Research Institute
      • Varanasi, India, 221005
        • ORIANA Hospital
    • 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 to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult males or females aged 18-70 years.
  • Patients with Hypovolemic shock due to blood loss 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.
  • Body weight 45 kg - 85 kg.
  • Female subject is either: (1) Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or, (2) 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.

Exclusion Criteria:

  • Terminal illness
  • Development of any other terminal illness not associated with Hypovolemic shock due to blood loss during the 28 day observation period
  • Patient with severe brain injury or with a Glasgow Coma Scale (GCS) < 8
  • Type of injury is not known
  • Inability to obtain intravenous access
  • Known pregnancy
  • Cardiopulmonary resuscitation (CPR) before randomization
  • Presence of a do not resuscitate order
  • Patient taking beta adrenergic antagonists
  • Untreated tension pneumothorax
  • Untreated cardiac tamponade
  • Bilateral absent pupillary light reflex (both pupils fixed and dilated)
  • Patient is participating in another interventional study
  • 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
In addition to standard of care normal saline to be used as vehicle in the phase-II 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
In addition to standard of care PMZ-2010 to be used as an experimental drug in the phase-II study to assess its efficacy 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
Incidence of PMZ-2010 related adverse events
Time Frame: 28 days
The primary objective of the study is to determine incidence of drug (PMZ-2010) related adverse events.
28 days

Secondary 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
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
Volume of blood products administered
Time Frame: 48 hours
Total volume of blood products administered - Mean through 48 hours
48 hours
Change in platelet count
Time Frame: 48 hours
Change in platelet count as part of coagulation parameters mean through 48 hours. Platelets are parts of the blood that helps the blood clot. Average platelet counts are 150,000 to 450,000 number of platelets per microliter.
48 hours
Change in prothrombin time
Time Frame: 48 hours
Change in prothrombin time as part of coagulation parameters mean through 48 hours. Prothrombin time (PT) is a blood test that measures the time it takes for the blood to clot. The average time range for blood to clot is about 10 to 14 seconds.
48 hours
Change in international normalized ratio (INR)
Time Frame: 48 hours
Change in international normalized ratio (INR) as part of coagulation parameters mean through 48 hours. The results of the prothrombin time test vary from laboratory to laboratory, therefore, a ratio called the international normalized ratio (INR) is calculated. It allows for differences in laboratories across the world so that test results become more relevant and can be compared. The average INR range is 0.8 to 1.1.
48 hours
Change in fibrinogen
Time Frame: 48 hours
Change in fibrinogen as part of coagulation parameters mean through 48 hours. Fibrinogen is a protein, specifically a clotting factor (factor I), that is essential for proper blood clot formation. The reference range for fibrinogen is 150-400 mg/dL
48 hours

Collaborators and Investigators

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

Sponsor

Pharmazz, Inc.

Investigators

  • Study Chair: Anil Gulati, 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)

May 29, 2017

Primary Completion (Actual)

September 19, 2018

Study Completion (Actual)

October 21, 2018

Study Registration Dates

First Submitted

August 11, 2019

First Submitted That Met QC Criteria

August 13, 2019

First Posted (Actual)

August 14, 2019

Study Record Updates

Last Update Posted (Actual)

August 14, 2019

Last Update Submitted That Met QC Criteria

August 13, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PMZ-02 Version 03 2017
  • CTRI/2017/03/008184 (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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