Polydatin Injectable (HW6) for Shock Treatment (PIST)

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

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.

Study Overview

• Status: Unknown
• Conditions: Shock, Septic; Shock, Hemorrhagic; Shock, Traumatic
• Intervention / Treatment: Drug: Polydatin Injectable

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Polydatin Injectable (HW6); 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; 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.; Other Names: HW6
PLACEBO_COMPARATOR: HW6 blank dummy (0.9%NaCl); 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?

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

Other Outcome Measures

Outcome Measure	Time Frame
Fluid intake and output volume	Every 24h for 5 days

Collaborators and Investigators

• Sponsor: Neptunus Pharmaceuticals Inc.
• Investigators: Study Chair: YU Lin, PhD, Neptunus Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (ANTICIPATED): September 1, 2014
• Study Completion (ANTICIPATED): December 1, 2014

Study Registration Dates

• First Submitted: January 29, 2013
• First Submitted That Met QC Criteria: January 29, 2013
• First Posted (ESTIMATE): January 30, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): January 30, 2013
• Last Update Submitted That Met QC Criteria: January 29, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Wounds and Injuries; Hemorrhage; Sepsis; Shock, Septic; Shock; Shock, Hemorrhagic; Shock, Traumatic
• Other Study ID Numbers: HW6-01-US (REGISTRY: Neptunus Pharmaceuticals, Inc.)