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

Sponsor
Pharmazz, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04045327
Collaborator
(none)
105
Enrollment
18
Locations
2
Arms
7.9
Actual Duration (Months)
5.8
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Normal saline + Standard Treatment
  • Drug: Centhaquine + Standard Treatment
 Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
105 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jan 31, 2019
Actual Primary Completion Date :
Sep 23, 2019
Actual Study Completion Date :
Sep 27, 2019

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in systolic and diastolic blood pressure [48 hours]

      Change in systolic and diastolic blood pressure - Mean through 48 hours

    2. Change in blood lactate level [48 hours]

      Change in blood lactate level - Mean through 48 hours

    3. Change in base-deficit [48 hours]

      Change in Base-deficit - Mean through 48 hours

    Secondary Outcome Measures

    1. Total Urine Output [48 hours]

      Total volume of urine output - Mean through 48 hours

    2. Vasopressor(s) infused [48 hours]

      Amount of total vasopressor(s) infused - Mean through 48 hours

    3. Volume of fluid administered [48 hours]

      Total volume of fluid administered - Mean through 48 hours

    4. Doses of study drug [48 hours]

      Number of doses of study drug administered in first 48 hours post randomization

    5. Incidence of mortality [28 days]

      Proportion of patients with all-cause mortality at 48 hours and 28 days

    6. Stay in hospital, in ICU and/or on Ventilator [28 days]

      Days in hospital, in ICU and/or on Ventilator - Mean through 28 days

    7. Change in Multiple Organ Dysfunction Syndrome Score [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.

    8. Change in Acute Respiratory Distress Syndrome [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.

    9. Change in Glasgow coma score [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.

    10. Incidence of adverse events [28 days]

      Proportion of patients with drug related adverse events during 28 days

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Seven Star Hospital Nagpur Maha India
    2 Jawahar Lal Nehru Medical College & Attached Hospitals Ajmer India 305001
    3 Radiant Superspeciality Hospital Amravati India 444606
    4 People Tree Hospitals Bangalore India 560022
    5 KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre Belgaum India 590010
    6 Shri Guru Ram Rai Institute of Medical & Health Sciences Dehradun India 248001
    7 Department of Surgery, GSVM Medical College Kanpur India 208002
    8 Institute of Postgraduate Medical Education & Research and SSKM Hospital Kolkata India 700020
    9 King George's Medical University Lucknow India 226003
    10 Christian Medical College & Hospital Ludhiana India 141008
    11 Sidhu Hospital Pvt. Ltd. Ludhiana India 141421
    12 Department of General Medicine, JSS Hospital Mysuru India 570004
    13 New Era Hospital & Research Institute Nagpur India 440008
    14 Rahate Surgical Hospital & ICU Nagpur India 440008
    15 Criticare Hospital & Research Institute Nagpur India 440012
    16 ACSR Government Medical College & Hospital Nellore India 524007
    17 Maulana Azad Medical College and associated Lok Nayak Hospital New Delhi India 110002
    18 Institute of Medical Sciences, Banaras Hindu University Varanasi India 221005

    Sponsors and Collaborators

    • Pharmazz, Inc.

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Pharmazz, Inc.
    ClinicalTrials.gov Identifier:
    NCT04045327
    Other Study ID Numbers:
    • PMZ-2010/CT-3.1/2018
    • CTRI/2019/01/017196
    First Posted:
    Aug 5, 2019
    Last Update Posted:
    Oct 4, 2019
    Last Verified:
    Oct 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Shock
    Hypovolemia

    Study Results

    No Results Posted as of Oct 4, 2019