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

NCT ID: NCT04056065

Last Updated: 2019-08-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-29

Study Completion Date

2018-10-21

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Hypovolemic Shock Blood Loss

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Normal Saline

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Centhaquine

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Vehicle PMZ-2010

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pharmazz, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anil Gulati

Role: STUDY_CHAIR

Pharmazz, Inc.

Locations

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Seven Star Hospital

Nagpur, Maha, India

Site Status

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

Belagavi, , India

Site Status

Post Graduate Institute of Medical Education and Research

Chandigarh, , India

Site Status

Institute of Postgraduate Medical Education & Research and SSKM Hospital

Kolkata, , India

Site Status

Dayanand Medical College & Hospital

Ludhiana, , India

Site Status

New Era Hospital & Research Institute

Nagpur, , India

Site Status

ORIANA Hospital

Varanasi, , India

Site Status

Countries

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India

References

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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.

Reference Type BACKGROUND
PMID: 30006694 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28385449 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26216751 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23871440 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22964270 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22487389 (View on PubMed)

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.

Reference Type 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.

Reference Type DERIVED
PMID: 33970455 (View on PubMed)

Other Identifiers

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CTRI/2017/03/008184

Identifier Type: REGISTRY

Identifier Source: secondary_id

PMZ-02 Version 03 2017

Identifier Type: -

Identifier Source: org_study_id

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