Polydatin Injectable (HW6) for Shock Treatment

Study Overview
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Brief Summary
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HW6 can prolong animal's survival time and increase the survival rate. HW6 enhances cardiac function, improves microcirculation, and increases blood pressure and pulse pressure, and improves blood perfusion of important organs; HW6's anti-shock activity comes from a combined multiple target pharmacological effects. Based on a completed phase II trial conducted in China, HW6 can effectively treatment shock patient. This is a phase II clinical study to further evaluate the efficacy and safety of Polydatin Injectable 100mg/5mL/via (HW6) in the treatment of shock in the United States. Patients with traumatic/hemorrhagic shock or septic shock admitted to the emergency room or ICU with systolic blood pressure < 90mmHg, or is on vasopressor(s) for systolic blood pressure stabilization, regardless the types of completed, on-going, or projected Standard of Care or surgery will be recruited to participant in the trial. A total of 120 patients with traumatic/hemorrhagic shock and 120 patients with septic shock will be enrolled. For each type of shock, sixty patients each will be in test group and control group. Both adult males and females aged 18-80 years are eligible. The primary clinical endpoint is the time length (TL) between the start of HW6 administration to the onset of the first treatment success, that is: the systolic blood pressure is stabilized at ≥90mmHg and MAP≥65mmHg for 1 hour without the use of vasopressors. Several secondary endpoints and biomarkers will be measured. Efficacy data will be compared using group t-test or Wilcoxon log-rank test between treatment groups and placebo groups. Safety data will also be reported accordingly.

Official Title
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A Randomized, Double-Blind, Placebo Controlled, Parallel Group Multi-Center Phase II Clinical Study to Evaluate the Efficacy and Safety of HW6 in the Treatment of Traumatic/Hemorrhagic Shock and Septic Shock

Conditions
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Shock, Hemorrhagic, Shock, Traumatic, Shock, Septic

Intervention / Treatment
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* Drug: Polydatin Injectable


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males or females aged 18-80 years. Patients with traumatic/hemorrhagic shock or septic shock admitted to the emergency room or ICU with systolic blood pressure < 90mmHg, or is on vasopressor(s) for systolic blood pressure stabilization, regardless the types of completed, ongoing, or projected Standard of Care or surgery. Patients (or its relative) who have signed Informed Consent Form to voluntarily participate in this clinical study. Exclusion Criteria: Has known allergic constitution or history of alcohol or drug allergy. or Complicating acute cardiac failure, acute renal failure, acute liver failure or disseminated intravascular coagulation (DIC). or Pregnant or lactating women. or Complicating moderate to severe craniocerebral injury. or Has known previous severe chronic disease(s) in liver, kidney, carvascualr system or central nervous system. or

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polydatin Injectable (HW6)<br>10ml(2 ampoules) diluted in 500ml of 0.9% NaCl solution for i.v. infusion over 2 hours; once daily for 5 consecutive days | Drug: Polydatin Injectable<br>* Dilute two 100mg/5mL vials of HW6 into 500mL 0.9% NaCl injection and administer as i.v. infusion over 2 hours. The drug should be given as early as possible right after the IC Form is signed on Day 1, and once every 24 hours for additional 4 doses.<br>* Other names: HW6;|
| Placebo Comparator: HW6 blank dummy (0.9%NaCl)<br>10ml (2 ampoules) diluted in 500ml of 0.9% NaCl solution for i.v. infusion over 2 hours; once daily for 5 consecutive days | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time length (TL) between the start of HW6 administration to the onset of the first TS. | Treatment success (TS): the systolic blood pressure is stabilized at ≥90mmHg and MAP≥65mmHg for 1 hour without the use of vasopressor(s). Blood pressure will be recorded every 10 min. Treatment success is considered to have been achieved when 7 consecutive systolic blood pressure to be≥90mmHg and MAP≥65mmHg. The TL is the time from the start of drug administration to the onset of TS (OTS) where the first systolic blood pressure≥90mmHg and MAP≥65mmHg is observed in the 7 consecutive measures. Blood pressure will be measured every hour after the TS. If blood pressure become unstable, standard care will be in practice. | From the start of drug administration to the onset of TS (OTS) where the first systolic blood pressure≥90mmHg and MAP≥65mmHg is observed in the 7 consecutive measures | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount and duration of total vasopressor(s) used during this TL period | Observation period: From start of study drug treatment to OTS. Record the details of the use of vasopressor(s) during TL for each subject, including name of medication, infusion concentration and rate, and the duration of each concentration and rate being maintained. Duration of vasopressor(s) use: accurate to the minute, or by the cumulative time of each administration if used intermittently. Total dose of vasopressor(s)：The total dose of each vasopressor. | From the start of drug administration to the onset of TS (OTS) where the first systolic blood pressure≥90mmHg and MAP≥65mmHg is observed in the 7 consecutive measures | 
| The degree of fluid dependence |  | from the start of testing drug to the OTS | 
| Metabolic indicators | Arterial blood lactate, lactate clearance, oxygen saturation mixed venous blood, blood gas levels | Within 6 days | 
| Severity of organ dysfunction in the ICU | Compare the changes in SOFA score during the administration stay between the two groups to assess the protective effect of the study drug on vital organs. | Daily during the administration stay after enrollment | 
| Duration of ICU stay |  | The total time (in hours) of ICU admission from the day of administration to day 7 (7 days) | 
| 28-day survival |  | From the end of drug administration to Day 28 |