Efficacy of PMZ-2010 (Centhaquine) a Resuscitative Agent for Hypovolemic Shock
- Conditions
- Hypovolemic Shock
- Interventions
- Drug: Normal saline + Standard Treatment
- Registration Number
- NCT04045327
- Lead Sponsor
- Pharmazz, Inc.
- Brief Summary
This is a prospective, multi-centric, randomized, double-blind, parallel, controlled phase-III efficacy clinical study of PMZ-2010 therapy in patients with hypovolemic shock.
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.
- Detailed Description
Approximately 105 patients will be randomized 2:1 into 2 treatment groups after meeting the eligibility criteria. Total 70 patients will be enrolled in PMZ-2010 group (Group 1) and in Normal Saline group (Group 2) total 35 patients will be enrolled.
* Group 1: PMZ-2010 (Dose: 0.01 mg/kg) + Standard of care
* Group 2: Normal Saline (Dose: Equal volume) + Standard of care In both treatment groups, patients will be provided the standard of care. PMZ-2010 or Normal Saline will be administered intravenously after randomization to hypovolemic shock patients with systolic arterial blood pressure ≤ 90 mmHg at presentation and continue to receive standard Shock Treatment. In PMZ-2010 group, dose of PMZ-2010 (0.01 mg/kg) will be administered as an intravenous (IV) infusion over 1 hour in 100 mL of normal saline. Second dose of PMZ-2010 will be administered if SBP falls below or remains below or equal to 90 mmHg but not before 4 hours of previous dose and total doses per day (in 24 hours) will not exceed 3 doses. PMZ-2010 administration if needed will continue for two days post randomization. Minimum 1 dose or maximum 6 doses of PMZ-2010 will be administered within first 48 hours. post randomization. In Control group, single dose of equal volume of Normal Saline will be administered as intravenous (IV) infusion over 1 hour in 100 mL of normal saline post randomization. Condition of administration will remain same as for PMZ-2010 group. Each patient will be monitored closely throughout his/her hospitalization and will be followed until discharge from randomization. Each patient will be assessed for efficacy parameters over 28 days from randomization to a clinic visit.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 105
- Patients with hypovolemic shock 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).
- Development of any other terminal illness not associated with Hypovolemic shock during the 28-day observation period.
- Patient with altered consciousness not due to Hypovolemic shock.
- Known 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PMZ-2010 (centhaquine) Centhaquine + Standard Treatment Hypovolemic shock patients will be provided the standard of care. Following randomization PMZ-2010 (0.01 mg/kg) will be administered intravenously over 1 hour in 100 mL of normal saline. Normal Saline Normal saline + Standard Treatment 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.
- Primary Outcome Measures
Name Time Method Change in base-deficit 48 hours Change in Base-deficit - Mean through 48 hours
Change in systolic and diastolic blood pressure 48 hours Change in systolic and diastolic blood pressure - Mean through 48 hours
Change in blood lactate level 48 hours Change in blood lactate level - Mean through 48 hours
- Secondary Outcome Measures
Name Time Method Stay in hospital, in ICU and/or on Ventilator 28 days Days in hospital, in ICU and/or on Ventilator - Mean through 28 days
Change in Glasgow coma score 28 days Change in Glasgow coma score (GCS) - Mean through 28 days. GCS is a 15 point scale to assess the level of consciousness of patients where less than 3 is comatose state and 15 is fully awake.
Incidence of mortality 28 days Proportion of patients with all-cause mortality at 48 hours and 28 days
Total Urine Output 48 hours Total volume of urine output - Mean through 48 hours
Vasopressor(s) infused 48 hours Amount of total vasopressor(s) infused - Mean through 48 hours
Volume of fluid administered 48 hours Total volume of fluid administered - Mean through 48 hours
Change in Multiple Organ Dysfunction Syndrome Score 28 days Change in Multiple Organ Dysfunction Syndrome Score (MODS) - Mean through 28 days. MODS is a 5 grade scale from 0 to 4, where 0 is the best and 4 is the worst outcome.
Incidence of adverse events 28 days Proportion of patients with drug related adverse events during 28 days
Doses of study drug 48 hours Number of doses of study drug administered in first 48 hours post randomization
Change in Acute Respiratory Distress Syndrome 28 days Change in Acute Respiratory Distress Syndrome (ARDS) - Mean through 28 days. ARDS will be determined using Murray Score for Acute Lung Injury which is based upon radiological findings, oxygenation status, ventilation status of the patient. A lower score of 0 is the best and about 2.5 is the worst outcome.
Trial Locations
- Locations (18)
Seven Star Hospital
🇮🇳Nagpur, Maha, India
Radiant Superspeciality Hospital
🇮🇳Amravati, India
ACSR Government Medical College & Hospital
🇮🇳Nellore, India
Institute of Medical Sciences, Banaras Hindu University
🇮🇳Varanasi, India
KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
🇮🇳Belgaum, India
People Tree Hospitals
🇮🇳Bangalore, India
King George's Medical University
🇮🇳Lucknow, India
Sidhu Hospital Pvt. Ltd.
🇮🇳Ludhiana, India
Maulana Azad Medical College and associated Lok Nayak Hospital
🇮🇳New Delhi, India
Jawahar Lal Nehru Medical College & Attached Hospitals
🇮🇳Ajmer, India
Institute of Postgraduate Medical Education & Research and SSKM Hospital
🇮🇳Kolkata, India
Christian Medical College & Hospital
🇮🇳Ludhiana, India
Shri Guru Ram Rai Institute of Medical & Health Sciences
🇮🇳Dehradun, India
Department of Surgery, GSVM Medical College
🇮🇳Kanpur, India
Department of General Medicine, JSS Hospital
🇮🇳Mysuru, India
New Era Hospital & Research Institute
🇮🇳Nagpur, India
Rahate Surgical Hospital & ICU
🇮🇳Nagpur, India
Criticare Hospital & Research Institute
🇮🇳Nagpur, India