Back to resultsPMZ-2010 (Centhaquine) as a Resuscitative Agent for Hypovolemic Shock
Primary Purpose
Hypovolemic Shock, Blood Loss
Status
Completed
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Normal Saline
Centhaquine
Sponsored by
About this trial
This is an interventional treatment trial for Hypovolemic Shock focused on measuring Resuscitative agent, Vasopressor
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- Seven Star Hospital
- KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
- Post Graduate Institute of Medical Education and Research
- Institute of Postgraduate Medical Education & Research and SSKM Hospital
- Dayanand Medical College & Hospital
- New Era Hospital & Research Institute
- ORIANA Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Normal Saline
PMZ-2010 (centhaquine)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Incidence of PMZ-2010 related adverse events
The primary objective of the study is to determine incidence of drug (PMZ-2010) related adverse events.
Secondary Outcome Measures
Volume of fluid administered
Total volume of fluid administered - Mean through 48 hours
Volume of blood products administered
Total volume of blood products administered - Mean through 48 hours
Vasopressor(s) infused
Amount of total vasopressor(s) infused - Mean through 48 hours
Doses of study drug
Number of doses of study drug administered in first 48 hours post randomization
Change in systolic and diastolic blood pressure
Change in systolic and diastolic blood pressure - Mean through 48 hours
Change in blood lactate level
Change in blood lactate level - Mean through 48 hours
Change in base-deficit
Change in Base-deficit - Mean through 48 hours
Change in platelet count
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 prothrombin time
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 international normalized ratio (INR)
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 fibrinogen
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 Multiple Organ Dysfunction Syndrome Score
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.
Change in Acute Respiratory Distress Syndrome
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.
Change in Glasgow coma score
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.
Stay in hospital, in ICU and/or on Ventilator
Days in hospital, in ICU and/or on Ventilator - Mean through 28 days
Incidence of mortality
Proportion of patients with all-cause mortality at 48 hours and 28 days
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04056065
Brief Title
PMZ-2010 (Centhaquine) as a Resuscitative Agent for Hypovolemic Shock
Official Title
A Prospective, Multi-centric, Randomized, Double-blind, Parallel, Saline Controlled Phase II Safety and Efficacy Study of PMZ-2010 as a Resuscitative Agent for Hypovolemic Shock to be Used Along With Standard Shock Treatment.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
May 29, 2017 (Actual)
Primary Completion Date
September 19, 2018 (Actual)
Study Completion Date
October 21, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmazz, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypovolemic Shock, Blood Loss
Keywords
Resuscitative agent, Vasopressor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Normal Saline
Arm Type
Active Comparator
Arm Description
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.
Arm Title
PMZ-2010 (centhaquine)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Other Intervention Name(s)
Vehicle
Intervention Description
In addition to standard of care normal saline to be used as vehicle in the phase-II study to assess efficacy of PMZ-2010 as a resuscitative agent for hypovolemic shock
Intervention Type
Drug
Intervention Name(s)
Centhaquine
Other Intervention Name(s)
PMZ-2010
Intervention Description
In addition to standard of care PMZ-2010 to be used as an experimental drug in the phase-II study to assess its efficacy as a resuscitative agent for hypovolemic shock
Primary Outcome Measure Information:
Title
Incidence of PMZ-2010 related adverse events
Description
The primary objective of the study is to determine incidence of drug (PMZ-2010) related adverse events.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Volume of fluid administered
Description
Total volume of fluid administered - Mean through 48 hours
Time Frame
48 hours
Title
Volume of blood products administered
Description
Total volume of blood products administered - Mean through 48 hours
Time Frame
48 hours
Title
Vasopressor(s) infused
Description
Amount of total vasopressor(s) infused - Mean through 48 hours
Time Frame
48 hours
Title
Doses of study drug
Description
Number of doses of study drug administered in first 48 hours post randomization
Time Frame
48 hours
Title
Change in systolic and diastolic blood pressure
Description
Change in systolic and diastolic blood pressure - Mean through 48 hours
Time Frame
48 hours
Title
Change in blood lactate level
Description
Change in blood lactate level - Mean through 48 hours
Time Frame
48 hours
Title
Change in base-deficit
Description
Change in Base-deficit - Mean through 48 hours
Time Frame
48 hours
Title
Change in platelet count
Description
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.
Time Frame
48 hours
Title
Change in prothrombin time
Description
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.
Time Frame
48 hours
Title
Change in international normalized ratio (INR)
Description
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.
Time Frame
48 hours
Title
Change in fibrinogen
Description
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
Time Frame
48 hours
Title
Change in Multiple Organ Dysfunction Syndrome Score
Description
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.
Time Frame
28 days
Title
Change in Acute Respiratory Distress Syndrome
Description
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.
Time Frame
28 days
Title
Change in Glasgow coma score
Description
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.
Time Frame
28 days
Title
Stay in hospital, in ICU and/or on Ventilator
Description
Days in hospital, in ICU and/or on Ventilator - Mean through 28 days
Time Frame
28 days
Title
Incidence of mortality
Description
Proportion of patients with all-cause mortality at 48 hours and 28 days
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anil Gulati
Organizational Affiliation
Pharmazz, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Seven Star Hospital
City
Nagpur
State/Province
Maha
Country
India
Facility Name
KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
City
Belgaum
ZIP/Postal Code
590010
Country
India
Facility Name
Post Graduate Institute of Medical Education and Research
City
Chandigarh
ZIP/Postal Code
160012
Country
India
Facility Name
Institute of Postgraduate Medical Education & Research and SSKM Hospital
City
Kolkata
ZIP/Postal Code
700020
Country
India
Facility Name
Dayanand Medical College & Hospital
City
Ludhiana
ZIP/Postal Code
141001
Country
India
Facility Name
New Era Hospital & Research Institute
City
Nagpur
ZIP/Postal Code
440008
Country
India
Facility Name
ORIANA Hospital
City
Varanasi
ZIP/Postal Code
221005
Country
India
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Plan to publish the findings after completion of the study
Citations:
PubMed Identifier
30006694
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.
Results Reference
background
PubMed Identifier
28385449
Citation
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.
Results Reference
background
PubMed Identifier
26216751
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.
Results Reference
background
PubMed Identifier
23871440
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.
Results Reference
background
PubMed Identifier
22964270
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.
Results Reference
background
PubMed Identifier
22487389
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.
Results Reference
background
Citation
Anil Gulati, Dinesh Jain, Nilesh Agrawal, Prashant Rahate, Soumen Das, Rajat Chowdhuri, Deba Dhibar, Madhav Prabhu, Sameer Haveri, Rohit Agarwal, Manish Lavhale. Clinical Phase II Results Of PMZ-2010 (centhaquin) As A Resuscitative Agent For Hypovolemic Shock. Critical Care Medicine Volume 47, Issue 1, Page 12.
Results Reference
result
PubMed Identifier
33970455
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.
Results Reference
derived
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PMZ-2010 (Centhaquine) as a Resuscitative Agent for Hypovolemic Shock
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