PMZ-2010 (Centhaquine) as a Resuscitative Agent for Hypovolemic Shock
- Conditions
- Blood LossHypovolemic Shock
- Interventions
- Drug: Normal Saline
- Registration Number
- NCT04056065
- Lead Sponsor
- Pharmazz, Inc.
- Brief Summary
This is a prospective, multi-centric, randomized, double-blind, parallel, controlled phase-II efficacy clinical study of PMZ-2010 therapy in patients with hypovolemic shock.
Centhaquine is highly safe and well tolerated. Toxicological studies showed high safety margin in preclinical studies. Its safety and tolerability has been demonstrated in a human phase I study in 25 subjects (CTRI/2014/06/004647; NCT02408731).
- Detailed Description
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.
Unlike presently used vasopressors, centhaquine increased mean arterial pressure by increasing stroke volume and cardiac output, and it decreased systemic vascular resistance. The most common adverse effects of vasopressors as a class include arrhythmias, fluid extravasation, and ischemia. Centhaquine does NOT act on beta-adrenergic receptors, and therefore the risk of arrhythmias is mitigated. It is NOT a vasopressor; however, it increases blood pressure and cardiac output by augmenting venous blood return to the heart and enhanced tissue perfusion by arterial dilatation. Enhancing tissue perfusion is a significant advantage over existing vasopressors.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- Adult males or females aged 18-70 years.
- Patients with Hypovolemic shock due to blood loss admitted to the emergency room or ICU with systolic blood pressure ≤ 90 mmHg at presentation and continue to receive standard shock treatment (endotracheal intubation; fluid resuscitation and vasopressors). Standard of care to be provided to the patients shall be the one used in the particular hospital setup.
- Body weight 45 kg - 85 kg.
- Female subject is either: (1) Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or, (2) If of childbearing potential, agrees to use any of the following effective separate forms of contraception throughout the study, up to and including the follow-up visits: Condoms, sponge, foams, jellies, diaphragm or intrauterine device, or A vasectomised partner OR abstinence.
- Terminal illness
- Development of any other terminal illness not associated with Hypovolemic shock due to blood loss during the 28 day observation period
- Patient with severe brain injury or with a Glasgow Coma Scale (GCS) < 8
- Type of injury is not known
- Inability to obtain intravenous access
- Known pregnancy
- Cardiopulmonary resuscitation (CPR) before randomization
- Presence of a do not resuscitate order
- Patient taking beta adrenergic antagonists
- Untreated tension pneumothorax
- Untreated cardiac tamponade
- Bilateral absent pupillary light reflex (both pupils fixed and dilated)
- 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 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 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 Incidence of PMZ-2010 related adverse events 28 days The primary objective of the study is to determine incidence of drug (PMZ-2010) related adverse events.
- Secondary Outcome Measures
Name Time Method Doses of study drug 48 hours Number of doses of study drug administered in first 48 hours post randomization
Vasopressor(s) infused 48 hours Amount of total vasopressor(s) infused - Mean through 48 hours
Change in fibrinogen 48 hours Change in fibrinogen as part of coagulation parameters mean through 48 hours. Fibrinogen is a protein, specifically a clotting factor (factor I), that is essential for proper blood clot formation. The reference range for fibrinogen is 150-400 mg/dL
Change in platelet count 48 hours Change in platelet count as part of coagulation parameters mean through 48 hours. Platelets are parts of the blood that helps the blood clot. Average platelet counts are 150,000 to 450,000 number of platelets per microliter.
Change in international normalized ratio (INR) 48 hours Change in international normalized ratio (INR) as part of coagulation parameters mean through 48 hours. The results of the prothrombin time test vary from laboratory to laboratory, therefore, a ratio called the international normalized ratio (INR) is calculated. It allows for differences in laboratories across the world so that test results become more relevant and can be compared. The average INR range is 0.8 to 1.1.
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.
Incidence of mortality 28 days Proportion of patients with all-cause mortality at 48 hours and 28 days
Change in blood lactate level 48 hours Change in blood lactate level - 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.
Volume of blood products administered 48 hours Total volume of blood products administered - Mean through 48 hours
Change in prothrombin time 48 hours Change in prothrombin time as part of coagulation parameters mean through 48 hours. Prothrombin time (PT) is a blood test that measures the time it takes for the blood to clot. The average time range for blood to clot is about 10 to 14 seconds.
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.
Volume of fluid administered 48 hours Total volume of fluid administered - 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 base-deficit 48 hours Change in Base-deficit - Mean through 48 hours
Stay in hospital, in ICU and/or on Ventilator 28 days Days in hospital, in ICU and/or on Ventilator - Mean through 28 days
Trial Locations
- Locations (7)
KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
🇮🇳Belgaum, India
Dayanand Medical College & Hospital
🇮🇳Ludhiana, India
ORIANA Hospital
🇮🇳Varanasi, India
Seven Star Hospital
🇮🇳Nagpur, Maha, India
New Era Hospital & Research Institute
🇮🇳Nagpur, India
Post Graduate Institute of Medical Education and Research
🇮🇳Chandigarh, India
Institute of Postgraduate Medical Education & Research and SSKM Hospital
🇮🇳Kolkata, India