NCT04056065

Brief Summary

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).

Trial Health

87
On Track

Trial Health Score

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

Enrollment
50

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started May 2017

Shorter than P25 for phase_2

Geographic Reach
1 country

7 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

May 29, 2017

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 19, 2018

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

October 21, 2018

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

August 11, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 14, 2019

Completed
Last Updated

August 14, 2019

Status Verified

August 1, 2019

Enrollment Period

1.3 years

First QC Date

August 11, 2019

Last Update Submit

August 13, 2019

Conditions

Hypovolemic ShockBlood Loss

Keywords

Resuscitative agentVasopressor

Outcome Measures

Primary Outcomes (1)

  • Incidence of PMZ-2010 related adverse events

    The primary objective of the study is to determine incidence of drug (PMZ-2010) related adverse events.

    28 days

Secondary Outcomes (16)

  • Volume of fluid administered

    48 hours

  • Volume of blood products administered

    48 hours

  • Vasopressor(s) infused

    48 hours

  • Doses of study drug

    48 hours

  • Change in systolic and diastolic blood pressure

    48 hours

  • +11 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

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

Interventions

Normal SalineDRUG

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

Also known as: Vehicle
Normal Saline
CenthaquineDRUG

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

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

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Seven Star Hospital

Nagpur, Maha, India

Location

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

Belagavi, 590010, India

Location

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

Location

Institute of Postgraduate Medical Education & Research and SSKM Hospital

Kolkata, 700020, India

Location

Dayanand Medical College & Hospital

Ludhiana, 141001, India

Location

New Era Hospital & Research Institute

Nagpur, 440008, India

Location

ORIANA Hospital

Varanasi, 221005, India

Location

Related Publications (8)

  • 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, Jain D, Agrawal NR, Rahate P, Choudhuri R, Das S, Dhibar DP, Prabhu M, Haveri S, Agarwal R, Lavhale MS. Resuscitative Effect of Centhaquine (Lyfaquin(R)) in Hypovolemic Shock Patients: A Randomized, Multicentric, Controlled Trial. Adv Ther. 2021 Jun;38(6):3223-3265. doi: 10.1007/s12325-021-01760-4. Epub 2021 May 10.

    PMID: 33970455DERIVED

MeSH Terms

Conditions

ShockHemorrhage

Interventions

Saline Solutioncenthaquine

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Officials

  • Anil Gulati

    Pharmazz, Inc.

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
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

August 11, 2019

First Posted

August 14, 2019

Study Start

May 29, 2017

Primary Completion

September 19, 2018

Study Completion

October 21, 2018

Last Updated

August 14, 2019

Record last verified: 2019-08

Data Sharing

IPD Sharing
Will not share

Plan to publish the findings after completion of the study

Locations

IN(7)