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

NCT05251181 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: Centhaquine/CT-3.2/2021
• Study Type: interventional
• Target: 430
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Hypovolemic Shock

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with all-cause mortality [Time frame: Day 0 through day 28].

  Incidence of mortality

  Day 0 through day 28

Secondary Outcomes (4)

• Proportion of subjects with all-cause mortality within 48 hours

  48 hours

• Change in Mean Arterial Pressure (MAP) from baseline of at least 10 mm Hg; Mean through 48 hours and at the time of discharge or day 7

  First 48 hours and at the time of discharge or day 7

• Time (hours) to decrease blood lactate level to <2 mmol/L

  48 hours

• Proportion of patients with adverse events (AEs) and serious adverse events (SAEs)

  Day 0 through day 28

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

Centhaquine

EXPERIMENTAL

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.

Drug: Centhaquine

Interventions

Normal Saline 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

Also known as: Vehicle

Normal saline

Centhaquine DRUG

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

Also known as: PMZ-2010

Centhaquine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males or females aged 18 years or older.
• 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.
• Blood lactate level indicative of hypovolemic shock with lactate level more than 2 mmol/L.

You may not qualify if:

• Subject with illness clinically defined as septic shock (Procalcitonin plasma levels of ≥0.5 ng/mL) or cardiogenic shock or neurogenic shock.
• Subject for whom an etiology for hypovolemic shock cannot be determined on initial evaluation.
• Hypovolemic shock due to traumatic brain injury, traumatic tamponade, traumatic tension pneumothorax, ventricular wall rupture.
• Patient with altered consciousness not due to hypovolemic shock.
• Subject with confirmed 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.

Sponsors & Collaborators

• Pharmazz, Inc.: lead

Related Publications (15)

• 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.

  PMID: 36726848 BACKGROUND

• 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.

  PMID: 36769755 BACKGROUND

• 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.

  PMID: 38542464 BACKGROUND

• 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.

  PMID: 38999331 BACKGROUND

• 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: 34061314 BACKGROUND

• 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: 33970455 BACKGROUND

• 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: 30006694 BACKGROUND

• 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.

  PMID: 34012389 BACKGROUND

• 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: 28385449 BACKGROUND

• 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.

  PMID: 27109141 BACKGROUND

• 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.

  PMID: 26725913 BACKGROUND

• 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: 26216751 BACKGROUND

• 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: 23871440 BACKGROUND

• 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: 22964270 BACKGROUND

• 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: 22487389 BACKGROUND

MeSH Terms

Conditions

Shock

Interventions

Saline Solution; centhaquine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Anil Gulati, MD, PhD

CONTACT

6307806087; anil.gulati@pharmazz.com

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: February 11, 2022
• First Posted: February 22, 2022
• Study Start: February 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 30, 2025

Record last verified: 2025-12