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

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ClinicalTrials.gov Identifier: NCT04045327
Recruitment Status : Recruiting
First Posted : August 5, 2019
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Pharmazz, Inc.

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
Hypovolemic Shock 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : January 31, 2019
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

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 Name: 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 Name: PMZ-2010




Primary Outcome Measures :
  1. Change in systolic and diastolic blood pressure [ Time Frame: 48 hours ]
    Change in systolic and diastolic blood pressure - Mean through 48 hours

  2. Change in blood lactate level [ Time Frame: 48 hours ]
    Change in blood lactate level - Mean through 48 hours

  3. Change in base-deficit [ Time Frame: 48 hours ]
    Change in Base-deficit - Mean through 48 hours


Secondary Outcome Measures :
  1. Total Urine Output [ Time Frame: 48 hours ]
    Total volume of urine output - Mean through 48 hours

  2. Vasopressor(s) infused [ Time Frame: 48 hours ]
    Amount of total vasopressor(s) infused - Mean through 48 hours

  3. Volume of fluid administered [ Time Frame: 48 hours ]
    Total volume of fluid administered - Mean through 48 hours

  4. Doses of study drug [ Time Frame: 48 hours ]
    Number of doses of study drug administered in first 48 hours post randomization

  5. Incidence of mortality [ Time Frame: 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 [ Time Frame: 28 days ]
    Days in hospital, in ICU and/or on Ventilator - Mean through 28 days

  7. 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.

  8. 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.

  9. 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.

  10. Incidence of adverse events [ Time Frame: 28 days ]
    Proportion of patients with drug related adverse events during 28 days



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04045327


Contacts
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Contact: Manish Lavhale, PhD 6307806087 manish.lavhale@pharmazz.com
Contact: Abhishek Singh abhishek.singh@pharmazz.com

Locations
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India
Seven Star Hospital Completed
Nagpur, Maha, India
Jawahar Lal Nehru Medical College & Attached Hospitals Recruiting
Ajmer, India, 305001
Contact: Veer B Singh       vbsingh2@rediffmail.com   
Principal Investigator: Sanjiv Maheshwari         
Radiant Superspeciality Hospital Recruiting
Amravati, India, 444606
Contact: Anand Kakani       kakani_anand@yahoo.co.in   
People Tree Hospitals Recruiting
Bangalore, India, 560022
Contact: Mohan Kamaraju       drmohan@peopletreehospitals.com   
KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre Recruiting
Belgaum, India, 590010
Contact: Sameer Haveri       drsameerhaveri@gmail.com   
Shri Guru Ram Rai Institute of Medical & Health Sciences Recruiting
Dehradun, India, 248001
Contact: Amit Varma       Dr_amitvarma2002@yahoo.com   
Department of Surgery, GSVM Medical College Recruiting
Kanpur, India, 208002
Contact: Sanjay Kala       drkala@yahoo.com   
Institute of Postgraduate Medical Education & Research and SSKM Hospital Recruiting
Kolkata, India, 700020
Contact: Rajat Choudhuri       rajat.choudhuri@gmail.com   
King George's Medical University Recruiting
Lucknow, India, 226003
Contact: G.P. Singh       gpsinghkgmu@gmail.com   
Christian Medical College & Hospital Recruiting
Ludhiana, India, 141008
Contact: Parvez D Haque       pdhaque@gmail.com   
Sidhu Hospital Pvt. Ltd. Recruiting
Ludhiana, India, 141421
Contact: Gursaran K Sidhu       gursaransidhu@gmail.com   
Department of General Medicine, JSS Hospital Recruiting
Mysuru, India, 570004
Contact: Mahesh M Mahesh       doctmahesh@yahoo.com   
New Era Hospital & Research Institute Recruiting
Nagpur, India, 440008
Contact: Nilesh R Agrawal       anileshr@gmail.com   
Rahate Surgical Hospital & ICU Recruiting
Nagpur, India, 440008
Contact: Aditya R Bothra       ady8181@gmail.com   
Criticare Hospital & Research Institute Recruiting
Nagpur, India, 440012
Contact: Deepak R Jeswani       deepakjeswani@yahoo.co.in   
ACSR Government Medical College & Hospital Recruiting
Nellore, India, 524007
Contact: S.K. Naushad Ali       mddbnoal@gmail.com   
Maulana Azad Medical College and associated Lok Nayak Hospital Recruiting
New Delhi, India, 110002
Contact: Anurag Mishra       anurag.alok@gmail.com   
Institute of Medical Sciences, Banaras Hindu University Recruiting
Varanasi, India, 221005
Contact: Saurabh Singh       saurabhrpsingh@gmail.com   
Sponsors and Collaborators
Pharmazz, Inc.
Investigators
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Study Chair: Anil Gulati, MD, PhD Pharmazz, Inc.

Publications of Results:
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 Shock. Critical Care Medicine Volume 47, Issue 1, Page 12.

Other Publications:

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Responsible Party: Pharmazz, Inc.
ClinicalTrials.gov Identifier: NCT04045327     History of Changes
Other Study ID Numbers: PMZ-2010/CT-3.1/2018
CTRI/2019/01/017196 ( Registry Identifier: Clinical Trials Registry - India )
First Posted: August 5, 2019    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Plan to publish the findings after completion of the study

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Shock
Hypovolemia
Pathologic Processes