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

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Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hypovolemic Shock Blood Loss

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

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (7)

Seven Star Hospital

Nagpur, Maha, India

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

Belagavi, India

Post Graduate Institute of Medical Education and Research

Chandigarh, India

Institute of Postgraduate Medical Education & Research and SSKM Hospital

Kolkata, India

Outcomes

Primary Outcomes

Incidence of PMZ-2010 related adverse events

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

Time frame: 28 days

Secondary Outcomes

Volume of fluid administered

Total volume of fluid administered - Mean through 48 hours

Time frame: 48 hours

Volume of blood products administered

Total volume of blood products administered - Mean through 48 hours

Time frame: 48 hours

Vasopressor(s) infused

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

Time frame: 48 hours

Doses of study drug

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

Time frame: 48 hours

Change in systolic and diastolic blood pressure

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

Time frame: 48 hours

Change in blood lactate level

Change in blood lactate level - Mean through 48 hours

Time frame: 48 hours

Change in base-deficit

Change in Base-deficit - Mean through 48 hours

Time frame: 48 hours

Change in platelet count

Data from ClinicalTrials.gov

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