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A Study to Assess Safety and Efficacy of Centhaquine as a Resuscitative Agent

NCT ID: NCT05251181

Last Updated: 2025-12-30

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

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

430 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-28

Study Completion Date

2027-10-31

Brief Summary

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This protocol is designed to develop a novel first-in-class treatment for use in critical care and life-threatening condition of hypovolemic shock with unmet need and is of national interest. Shock is a life-threatening condition of circulatory failure. It is a state of cellular and tissue hypoxia due to reduced oxygen delivery and/or increased oxygen consumption or inadequate oxygen utilization. Shock most commonly occurs when there is circulatory failure leading to reduced tissue perfusion. There are four types of shock: distributive, cardiogenic, hypovolemic, and obstructive. However, these are not exclusive, and many patients with circulatory failure have a combination of more than one form of shock (multifactorial shock).

Detailed Description

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Despite advances in medical science, treatments for hypovolemic shock have changed little in the past 30-40 years. A wounded soldier bleeding on the battlefield, or a trauma victim, is treated today largely as the patient would have been treated in 1970. The primary goal when treating traumatic hemorrhage is to control blood loss, support ventilation and oxygenation, and maintain cardiovascular function to preserve organ blood perfusion. Rapid volume repletion is indicated in patients with severe hypovolemic shock. Delayed therapy can lead to ischemic injury and possibly to irreversible shock and multiorgan system failure. Although resuscitation with intravenous fluids and blood products has remained the gold standard over the last twenty years, vigorous volume resuscitation may not be curative and has been associated with the development of serious complications including coagulopathy, acute lung injury, and abdominal compartment syndrome. Massive resuscitation also profoundly alters the neuroendocrine milieu needed to maintain vasomotor tone and may lead to a state of recalcitrant hypotension, multi-organ failure, and ultimately death in severely injured patients. Vasopressors are generally used to increase blood pressure and cardiac output, but sometimes they are not recommended since they do not correct the primary problem and tend to reduce tissue perfusion further.

This study seeks to address the impact of centhaquine on the patient population with hypovolemic shock (prehospital SBP ≤ 90 mmHg). The inclusion of centhaquine during resuscitation could potentially prevent the profound hypotension seen in late-stage shock, limit the need for aggressive volume and blood product resuscitation, and decrease the incidence of resuscitation-associated complications. This study will investigate if early use of centhaquine during the resuscitation of hypovolemic shock results in improved survival at Day 28, fewer blood transfusions, a decreased need for crystalloid resuscitation, and a lower incidence of resuscitation related complications.

In animal models of hypovolemic shock, low doses (0.006 to 0.05 mg/kg) of centhaquine proved to be highly effective in resuscitation. Centhaquine significantly decreased blood lactate and increased mean arterial pressure (MAP), pulse pressure, and cardiac output (CO), as well as decreased mortality and increased the survival time of animals with severe blood loss. Furthermore, its resuscitative effect was significantly greater compared to presently used resuscitative solutions. The proposed mechanism of action of centhaquine is that in low doses, it acts on α2B adrenergic receptors to produce venous constriction and a consequent increase in venous return to the heart, and stimulation of sodium sense in the brain to increase the intravascular blood volume. These effects increase cardiac output and tissue blood perfusion, which may be responsible for its resuscitative action.

Centhaquine has been found to be an effective resuscitative agent in rat, rabbit, and swine models of hemorrhagic shock. Its safety and tolerability have been demonstrated in a human phase I study in 25 subjects. Clinical phase II and III results indicate that centhaquine is a novel first-in-class, highly effective resuscitative agent for hypovolemic shock due to blood loss. Safety and highly significant efficacy in improving blood pressure, lactate levels, base deficit, and reduction in the use of vasopressors and reduced mortality obtained in phase II and III studies in patients of hypovolemic shock are convincing. Therefore, a phase III clinical study in the United States and Europe will be conducted in patients of hypovolemic shock patients.

The present multi-centric, randomized, double-blind, placebo-controlled phase-III study aims to assess the efficacy and safety of centhaquine as a resuscitative agent to be used as an adjuvant to standard treatment of hypovolemic shock.

Conditions

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Hypovolemic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a multi-centric, randomized, double-blind, placebo-controlled phase-III clinical study to assess the safety and efficacy of centhaquine therapy in patients with hypovolemic shock with systolic arterial blood pressure ≤ 90 mmHg at presentation and continue to receive standard treatment of shock.

This protocol is designed to develop a novel first-in-class treatment for use in critical care and life-threatening condition of hypovolemic shock with unmet need and is of national interest.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
In this double-blind study, the subject and all relevant personnel involved with the conduct and interpretation of the study (including investigator, investigational site personnel, and the sponsor or designee's staff) will remain blinded to the identity of the Investigational Product (IP) assigned and the randomization codes. The final randomization list will be kept strictly confidential, filed securely by the independent biostatistician, and accessible only to authorized persons as per the sponsor's standard operating procedures until the completion of the study.

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

Normal Saline to be Used as Vehicle in the Phase-III Study to Assess Efficacy of Centhaquine as a Resuscitative Agent for Hypovolemic Shock

Centhaquine

Hypovolemic shock patients will be provided the standard of care. Following randomization centhaquine (0.01 mg/kg) will be administered intravenously over 1 hour in 100 mL of normal saline.

Group Type EXPERIMENTAL

Centhaquine

Intervention Type DRUG

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

Interventions

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Normal Saline

Normal Saline to be Used as Vehicle in the Phase-III Study to Assess Efficacy of Centhaquine as a Resuscitative Agent for Hypovolemic Shock

Intervention Type DRUG

Centhaquine

Phase-III Study to Assess Efficacy of Centhaquine 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

A subject will be eligible for inclusion in the study if he/she fulfils the following criteria:

1. Adult males or females aged 18 years or older.
2. Subjects with hypovolemic shock admitted to the hospital with systolic blood pressure ≤ 90 mm Hg at presentation, Mean Arterial Pressor (MAP) ≤ 65 mm Hg and continue to receive standard treatment of shock (endotracheal intubation; fluid resuscitation and vasopressors). Standard of care to be provided to the subject shall be the one used in that hospital.
3. Blood lactate level indicative of hypovolemic shock with lactate level more than 2 mmol/L.

Exclusion Criteria

1. Subject with illness clinically defined as septic shock (Procalcitonin plasma levels of ≥0.5 ng/mL) or cardiogenic shock or neurogenic shock.
2. Subject for whom an etiology for hypovolemic shock cannot be determined on initial evaluation.
3. Hypovolemic shock due to traumatic brain injury, traumatic tamponade, traumatic tension pneumothorax, ventricular wall rupture.
4. Patient with altered consciousness not due to hypovolemic shock.
5. Subject with confirmed pregnancy.
6. Cardiopulmonary resuscitation (CPR) before randomization.
7. Presence of a do not resuscitate order.
8. Patient is participating in another interventional study.
9. 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

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

Central Contacts

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Anil Gulati, MD, PhD

Role: CONTACT

Phone: 6307806087

Email: [email protected]

References

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Geevarghese M 3rd, Patel K, Gulati A, Ranjan AK. Role of adrenergic receptors in shock. Front Physiol. 2023 Jan 16;14:1094591. doi: 10.3389/fphys.2023.1094591. eCollection 2023.

Reference Type BACKGROUND
PMID: 36726848 (View on PubMed)

Ranjan AK, Gulati A. Controls of Central and Peripheral Blood Pressure and Hemorrhagic/Hypovolemic Shock. J Clin Med. 2023 Jan 31;12(3):1108. doi: 10.3390/jcm12031108.

Reference Type BACKGROUND
PMID: 36769755 (View on PubMed)

Chalkias A, Pais G, Gulati A. Effect of Centhaquine on the Coagulation Cascade in Normal State and Uncontrolled Hemorrhage: A Multiphase Study Combining Ex Vivo and In Vivo Experiments in Different Species. Int J Mol Sci. 2024 Mar 20;25(6):3494. doi: 10.3390/ijms25063494.

Reference Type BACKGROUND
PMID: 38542464 (View on PubMed)

Khanna A, Vaidya K, Shah D, Ranjan AK, Gulati A. Centhaquine Increases Stroke Volume and Cardiac Output in Patients with Hypovolemic Shock. J Clin Med. 2024 Jun 27;13(13):3765. doi: 10.3390/jcm13133765.

Reference Type BACKGROUND
PMID: 38999331 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34061314 (View on PubMed)

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 BACKGROUND
PMID: 33970455 (View on PubMed)

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)

Ranjan AK, Zhang Z, Briyal S, Gulati A. Centhaquine Restores Renal Blood Flow and Protects Tissue Damage After Hemorrhagic Shock and Renal Ischemia. Front Pharmacol. 2021 May 3;12:616253. doi: 10.3389/fphar.2021.616253. eCollection 2021.

Reference Type BACKGROUND
PMID: 34012389 (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)

O'Donnell JN, O'Donnell EP, Kumar EJ, Lavhale MS, Andurkar SV, Gulati A, Scheetz MH. Pharmacokinetics of centhaquin citrate in a dog model. J Pharm Pharmacol. 2016 Jun;68(6):803-9. doi: 10.1111/jphp.12554. Epub 2016 Apr 25.

Reference Type BACKGROUND
PMID: 27109141 (View on PubMed)

O'Donnell JN, Gulati A, Lavhale MS, Sharma SS, Patel AJ, Rhodes NJ, Scheetz MH. Pharmacokinetics of centhaquin citrate in a rat model. J Pharm Pharmacol. 2016 Jan;68(1):56-62. doi: 10.1111/jphp.12498. Epub 2016 Jan 4.

Reference Type BACKGROUND
PMID: 26725913 (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)

Other Identifiers

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Centhaquine/CT-3.2/2021

Identifier Type: -

Identifier Source: org_study_id