A Study to Assess the Safety and Efficacy of Centhaquine in Hypovolemic Shock Patients

NCT05956418 | Recruiting Phase 4 DMC

• 1 other identifier: PMZ-2010/CT-4.1/2019
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 17

Brief Summary

This is a prospective, multi-centric, open-labeled, phase-IV clinical study to evaluate the safety and efficacy of centhaquine citrate (LYFAQUIN™), a first-in-class drug for treating hypovolemic shock, a life-threatening condition caused by severe blood or fluid loss. Centhaquine has been found to be an effective resuscitative agent in rat, rabbit, and swine models of hemorrhagic shock. It has demonstrated the ability to decrease blood lactate levels, increase mean arterial pressure, enhance cardiac output, and reduce mortality rates. The increase in cardiac output during resuscitation is primarily attributed to an augmentation in stroke volume. Centhaquine exerts its effects by acting on the venous α2B-adrenergic receptors, which enhances venous return to the heart. Additionally, it produces arterial dilation by targeting central α2A-adrenergic receptors, thereby reducing sympathetic activity and systemic vascular resistance.

Conditions

Hypovolemic Shock

Keywords

Shock; Hypovolemia; Hemorrhage; Blood Pressure; Resuscitation; Centhaquine; Adrenergic

Outcome Measures

Primary Outcomes (1)

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

  Any unfavorable sign, symptom, or disease that occurs while using centhaquine will be reported as an adverse event (AE), including worsening of pre-existing medical conditions. A severe medical occurrence, such as death, life-threatening situations, hospitalization, significant disability, or congenital anomalies will be reported as a serious adverse event (SAE). AEs will be collected through patient questioning, spontaneous reports, and observation. Description, severity, start and end dates, incidence, relationship to the centhaquine, seriousness, action taken, and outcome of AEs will be documented in source documents and case report forms (CRFs). All SAEs will be reported within 24 hours to the sponsor, Drugs Controller General of India, and the ethics committee. Follow-up information and hospitalization or autopsy reports will be provided if necessary. A detailed analyzed report of all SAEs will be prepared and submitted to relevant authorities within 14 days.

  Up to 7 days

Secondary Outcomes (10)

• Systolic and diastolic blood pressure

  Up to 7 days

• Blood lactate

  48 hours

• Base-deficit

  48 hours

• Time in intensive care unit (ICU)

  Up to 7 days

• Time on ventilator

  Up to 7 days

Study Arms (1)

Centhaquine (Dose: 0.01 mg/kg) + Standard of care

EXPERIMENTAL

Centhaquine will be administered intravenously after enrollment to hypovolemic shock patients with systolic arterial blood pressure ≤ 90 mmHg at presentation and continue to receive standard shock treatment. Centhaquine will be administered at a dose of 0.01 mg/kg of body weight, as an intravenous (IV) infusion over 1 hour in 100 mL of normal saline. Second dose of centhaquine will be administered if SBP falls below or remains below or equal to 90 mmHg but not before 4 hours of the previous dose and total doses per day (in 24 hours) will not exceed 3 doses. Centhaquine administration if needed will continue for two days post-enrollment. A minimum of 1 dose or maximum of 6 doses of centhaquine will be administered within first 48 hours post-enrollment. Each patient will be monitored closely throughout his/her hospitalization and will be followed until discharge or day 7 (whichever is earlier) from enrollment.

Drug: Centhaquine

Interventions

Centhaquine DRUG

Centhaquine (LYFAQUIN™ or centhaquine citrate) is a novel, first-in-class, highly effective resuscitative agent for hypovolemic shock. Phase II results demonstrate highly significant efficacy in improving blood pressure (p\<0.0001), lactate levels (p=0.0012) and base-deficit (p\<0.0001). There was also improvement in reduction in use of vasopressors and reduced mortality. Similarly, results of phase III study confirmed the safety and efficacy of centhaquine as an adjuvant to standard of care for hypovolemic shock. Therefore, to assess safety of centhaquine in large population a phase IV study (post-authorization safety study) has been designed.

Also known as: LYFAQUIN™, Centhaquine Citrate, 2-(2-(4-(3-methylphenyl)-1-piperazinyl)ethyl) quinoline citrate, PMZ-2010

Centhaquine (Dose: 0.01 mg/kg) + Standard of care

Eligibility Criteria

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

You may qualify if:

• Adult hypovolemic shock patients aged 18 years or older admitted to the emergency room or ICU with systolic blood pressure ≤ 90 mmHg at presentation and continue to receive standard shock treatment. Blood Lactate level indicative of hypovolemic shock (\>2.0 mmol/L).

You may not qualify if:

• Development of any other terminal illness not associated with hypovolemic shock during the study duration.
• Patient with altered consciousness not due to hypovolemic shock and comatose patient. • Known pregnancy.
• Cardiopulmonary resuscitation (CPR) before enrollment.
• 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 sepsis, cancer, chronic renal failure, liver failure, decompensated heart failure, or AIDS.

Sponsors & Collaborators

• Pharmazz, Inc.: lead

Study Sites (17)

ACSR Government Medical College and Hospital

Nellore, Andhra Pradesh, 524004, India

RECRUITING

All India Institute of Medical Sciences (AIIMS)

Raipur, Chhattisgarh, 492099, India

RECRUITING

Aman Hospital

Vadodara, Gujarat, 390021, India

RECRUITING

New Era Hospital

Nagpur, Maharashtra, 440008, India

RECRUITING

Seven Star Hospital

Nagpur, Maharashtra, 440009, India

RECRUITING

Meditrina Hospital

Nagpur, Maharashtra, 440012, India

RECRUITING

Sri Guru Ram Das University of Health Sciences (SGRDH)

Amritsar, Punjab, 143501, India

RECRUITING

Dayanand Medical College & Hospital (DMCH)

Ludhiana, Punjab, 141001, India

RECRUITING

Christian Medical College and Hospital (CMC)

Ludhiana, Punjab, 141008, India

RECRUITING

Government Medical College

Kota, Rajasthan, 324010, India

RECRUITING

KG Hospital

Coimbatore, Tamil Nadu, 641018, India

RECRUITING

Pushpanjali Hospital

Agra, Uttar Pradesh, 282002, India

RECRUITING

Maharani Laxmi Bai Medical College (MLBMC)

Jhānsi, Uttar Pradesh, 284001, India

RECRUITING

Nirmal Hospital

Jhānsi, Uttar Pradesh, 284128, India

RECRUITING

Ganesh Shankar Vidyarthi Memorial Medical College (GSVM)

Kanpur, Uttar Pradesh, 208002, India

RECRUITING

Janta Hospital

Varanasi, Uttar Pradesh, 221005, India

RECRUITING

IPGMER & SSKM Hospital

Kolkata, West Bengal, 700020,, India

RECRUITING

Related Publications (10)

• 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

• 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

• 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, 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

• 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

• 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

• 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

• 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

• 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 DERIVED

MeSH Terms

Conditions

Shock; Hypovolemia; Hemorrhage

Interventions

centhaquine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Manish Lavhale, Ph.D.

  Pharmazz India

  STUDY DIRECTOR

Central Study Contacts

Dharmesh Shah, Dr.

CONTACT

+91(120)256-9779; dharmesh.shah@pharmazz.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a prospective, multi-centric, open-labeled, single-arm and phase-IV study in 400 hypovolemic shock patients with a systolic arterial blood pressure ≤ 90 mmHg. The study duration will be approximately 15 months, including a 12-month enrollment period. All patients in the single group of the study will receive treatment with "Centhaquine (Dose: 0.01 mg/kg) + Standard of care." A second dose of centhaquine may be given if the systolic blood pressure remains low. However, the maximum number of doses per day should not exceed 3, and if needed the treatment will continue for the 2nd day of enrollment. Within the first 48 hours post-enrollment, a minimum of 1 dose and a maximum of 6 doses of centhaquine will be administered. Each patient will be closely monitored throughout their hospitalization and followed until discharge or day 7 (whichever comes earlier) from enrollment.

Study Record Dates

• First Submitted: June 30, 2023
• First Posted: July 21, 2023
• Study Start: August 13, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IN (17)