Hypovolemic Shock Clinical Trial
Official title:
A Prospective, Multi-centric, Open-labeled, Phase-IV Study to Assess Safety and Efficacy of LYFAQUIN™ (Centhaquine Citrate) as a Resuscitative Agent for Hypovolemic Shock to be Used as an Adjuvant to Standard Treatment of Shock
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.
Status | Recruiting |
Enrollment | 400 |
Est. completion date | December 2025 |
Est. primary completion date | November 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria • 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). Exclusion Criteria - 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. |
Country | Name | City | State |
---|---|---|---|
India | Pushpanjali Hospital | Agra | UP |
India | Sri Guru Ram Das University of Health Sciences (SGRDH) | Amritsar | Punjab |
India | KG Hospital | Coimbatore | Tamil Nadu |
India | Maharani Laxmi Bai Medical College (MLBMC) | Jhansi | UP |
India | Nirmal Hospital | Jhansi | UP |
India | Ganesh Shankar Vidyarthi Memorial Medical College (GSVM) | Kanpur | UP |
India | IPGMER & SSKM Hospital | Kolkata | West Bengal |
India | Government Medical College | Kota | Rajasthan |
India | Christian Medical College and Hospital (CMC) | Ludhiana | Punjab |
India | Dayanand Medical College & Hospital (DMCH) | Ludhiana | Punjab |
India | Meditrina Hospital | Nagpur | Maharashtra |
India | New Era Hospital | Nagpur | Maharashtra |
India | Seven Star Hospital | Nagpur | Maharashtra |
India | ACSR Government Medical College and Hospital | Nellore | Andhra Pradesh |
India | All India Institute of Medical Sciences (AIIMS) | Raipur | Chhattisgarh |
India | Aman Hospital | Vadodara | Gujarat |
India | Janta Hospital | Varanasi | UP |
Lead Sponsor | Collaborator |
---|---|
Pharmazz, Inc. |
India,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Systolic and diastolic blood pressure | Hypovolemia is known to cause low blood pressure, severely. That may lead to multi-organ failure or death. Hence, improving blood pressure is the key to the development of effective hypovolemic shock therapeutics. | Up to 7 days | |
Secondary | Blood lactate | Increased blood lactate level is indicative of hypovolemic shock. Lactate level of more than 2 mmol/L is correlated with increased tissue hypoxia and anaerobic respiration following shock. | 48 hours | |
Secondary | Base-deficit | The base deficit is a known measure of metabolic acidosis and has been advocated as a marker of resuscitation adequacy. It is correlated with the severity of injury and degree of hemorrhage, which makes it useful in the operating room (OR) as an endpoint of resuscitation. | 48 hours | |
Secondary | Time in intensive care unit (ICU) | In the intensive care unit, specific medical specialties will be provided to support the shock patients whose lives are in immediate danger. ICU medical interventions take over the function of defective or damaged organs and maintain blood pressure in shock patients. | Up to 7 days | |
Secondary | Time on ventilator | Ventilatory support is commonly used to resolve the circulation problem in shock patients. | Up to 7 days | |
Secondary | Urine output | The urine output is an important clinical parameter for renal function and blood volume status, especially in critically ill multiple trauma patients during their hospital admission and ICU. Also, it is a reliable incipient marker of hypovolemia therefore it has a place among the parameters used to monitor the hemodynamic status of critically ill multiple trauma patients. | 48 hours | |
Secondary | Incidence of mortality | The hypovolemic shock causes ischemic injury to vital organs and may lead to multi-system organ failure and death (mortality). | 7 days | |
Secondary | Multiple Organ Dysfunction Syndrome score (MODS) | Multiple organ dysfunction syndrome (MODS) is a life-threatening complication and a major cause of mortality in the injured patient. MODS is a 5-grade scale from 0 to 4, where 0 is the best and 4 is the worst outcome. | Up to 7 days | |
Secondary | Acute Respiratory Distress Syndrome (ARDS) | Acute respiratory distress syndrome (ARDS) is a serious lung condition, which causes low blood oxygen. It is a complication of shock associated with hypovolemia, hypoxemia, and inadequate cardiovascular compensatory responses to increased O2 demands. It is preceded by hypovolemia, reduced heart function, inadequate O2 delivery, and extraction needed to maintain VO2 in injured patients with increased metabolic as well as O2 requirements. | Up to 7 days | |
Secondary | Glasgow Coma Scale (GCS) | Glasgow Coma Scale (GCS) is a neurological scale consisting of the sum of three coded values: motor, verbal, and eye-opening. It provides a reliable way of recording the conscious state of a person or shock patient. GCS is a 15-point scale to assess the level of consciousness of patients where less than 3 is a comatose state and 15 is fully awake. | Up to 7 days |
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