NCT04045327

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
105

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jan 2019

Shorter than P25 for phase_3

Geographic Reach
1 country

18 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 31, 2019

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

July 31, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 5, 2019

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 23, 2019

Completed
4 days until next milestone

Study Completion

Last participant's last visit for all outcomes

September 27, 2019

Completed
Last Updated

October 4, 2019

Status Verified

October 1, 2019

Enrollment Period

8 months

First QC Date

July 31, 2019

Last Update Submit

October 3, 2019

Conditions

Hypovolemic Shock

Outcome Measures

Primary Outcomes (3)

  • Change in systolic and diastolic blood pressure

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

    48 hours

  • Change in blood lactate level

    Change in blood lactate level - Mean through 48 hours

    48 hours

  • Change in base-deficit

    Change in Base-deficit - Mean through 48 hours

    48 hours

Secondary Outcomes (10)

  • Total Urine Output

    48 hours

  • Vasopressor(s) infused

    48 hours

  • Volume of fluid administered

    48 hours

  • Doses of study drug

    48 hours

  • Incidence of mortality

    28 days

  • +5 more secondary outcomes

Study Arms (2)

Normal Saline

ACTIVE COMPARATOR

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

PMZ-2010 (centhaquine)

EXPERIMENTAL

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

Interventions

Normal saline + Standard TreatmentDRUG

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

Also known as: Vehicle
Normal Saline
Centhaquine + Standard TreatmentDRUG

Phase-III Study to Assess Efficacy of PMZ-2010 as a Resuscitative Agent for Hypovolemic Shock

Also known as: PMZ-2010
PMZ-2010 (centhaquine)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • Development of any other terminal illness not associated with Hypovolemic shock during the 28-day observation period.
  • Patient with altered consciousness not due to Hypovolemic shock.
  • Known pregnancy.
  • Cardiopulmonary resuscitation (CPR) before randomization.
  • Presence of a do not resuscitate order.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Seven Star Hospital

Nagpur, Maha, India

Location

Jawahar Lal Nehru Medical College & Attached Hospitals

Ajmer, 305001, India

Location

Radiant Superspeciality Hospital

Amravati, 444606, India

Location

People Tree Hospitals

Bangalore, 560022, India

Location

KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre

Belagavi, 590010, India

Location

Shri Guru Ram Rai Institute of Medical & Health Sciences

Dehradun, 248001, India

Location

Department of Surgery, GSVM Medical College

Kanpur, 208002, India

Location

Institute of Postgraduate Medical Education & Research and SSKM Hospital

Kolkata, 700020, India

Location

King George's Medical University

Lucknow, 226003, India

Location

Christian Medical College & Hospital

Ludhiana, 141008, India

Location

Sidhu Hospital Pvt. Ltd.

Ludhiana, 141421, India

Location

Department of General Medicine, JSS Hospital

Mysuru, 570004, India

Location

New Era Hospital & Research Institute

Nagpur, 440008, India

Location

Rahate Surgical Hospital & ICU

Nagpur, 440008, India

Location

Criticare Hospital & Research Institute

Nagpur, 440012, India

Location

ACSR Government Medical College & Hospital

Nellore, 524007, India

Location

Maulana Azad Medical College and associated Lok Nayak Hospital

New Delhi, 110002, India

Location

Institute of Medical Sciences, Banaras Hindu University

Varanasi, 221005, India

Location

Related Publications (9)

  • 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. 2019 Dec;45(6):1077-1085. doi: 10.1007/s00068-018-0980-1. Epub 2018 Jul 13.

    PMID: 30006694BACKGROUND

  • 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.

    PMID: 28385449BACKGROUND

  • 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.

    PMID: 26216751BACKGROUND

  • 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.

    PMID: 23871440BACKGROUND

  • 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.

    PMID: 22964270BACKGROUND

  • 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.

    PMID: 22487389BACKGROUND

  • 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.

    RESULT

  • Gulati A, Choudhuri R, Gupta A, Singh S, Ali SKN, Sidhu GK, Haque PD, Rahate P, Bothra AR, Singh GP, Maheshwari S, Jeswani D, Haveri S, Agarwal A, Agrawal NR. A Multicentric, Randomized, Controlled Phase III Study of Centhaquine (Lyfaquin(R)) as a Resuscitative Agent in Hypovolemic Shock Patients. Drugs. 2021 Jun;81(9):1079-1100. doi: 10.1007/s40265-021-01547-5. Epub 2021 Jun 1.

    PMID: 34061314DERIVED

  • Gulati A, Choudhuri R, Gupta A, Singh S, Noushad Ali SK, Sidhu GK, Haque PD, Rahate P, Bothra AR, Singh GP, Maheshwari S, Jeswani D, Haveri S, Agarwal A, Agrawal NR. A multicentric, randomized, controlled phase III study of centhaquine (Lyfaquin (R) ) as a resuscitative agent in hypovolemic shock patients. medRxiv [Preprint]. 2021 May 9:2020.07.30.20068114. doi: 10.1101/2020.07.30.20068114.

    PMID: 33173916DERIVED

MeSH Terms

Conditions

Shock

Interventions

Saline Solutioncenthaquine

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Officials

  • Anil Gulati, MD, PhD

    Pharmazz, Inc.

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 31, 2019

First Posted

August 5, 2019

Study Start

January 31, 2019

Primary Completion

September 23, 2019

Study Completion

September 27, 2019

Last Updated

October 4, 2019

Record last verified: 2019-10

Data Sharing

IPD Sharing
Will not share

Plan to publish the findings after completion of the study

Locations

IN(18)