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Trial record 1 of 6 for:    SHINE Trauma
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Infusion of Prostacyclin vs Placebo for 72-hours in Trauma Patients With Haemorrhagic Shock Suffering From Organ Failure (SHINE-TRAUMA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03903939
Recruitment Status : Recruiting
First Posted : April 4, 2019
Last Update Posted : March 9, 2020
Sponsor:
Collaborators:
Odense University Hospital
Aarhus University Hospital
Aalborg University Hospital
Oslo University Hospital
Information provided by (Responsible Party):
Pär Johansson, Rigshospitalet, Denmark

Tracking Information
First Submitted Date  ICMJE April 3, 2019
First Posted Date  ICMJE April 4, 2019
Last Update Posted Date March 9, 2020
Actual Study Start Date  ICMJE May 22, 2019
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
ICU free days [ Time Frame: 28 days after admission ]
Defined as the number of days spend alive out of the ICU to day 28. Patients who dies on or prior to day 28 during their initial ICU stay are assigned zero in ICU free days
Original Primary Outcome Measures  ICMJE
 (submitted: April 3, 2019)
ICU days [ Time Frame: Until day 90 ]
Number of ICU-free days during hospital admission
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
  • All-cause mortality [ Time Frame: 90 days after admission ]
    Vital status of the patient at day 28 and 90.
  • Hospital length of stay [ Time Frame: 90 days after admission ]
    Defined as the total number of days admitted to the hospital until day 90
  • Vasopressor free days [ Time Frame: 28 days after admission ]
    The number of calendar days between admission and 28 days later that the patients is alive and without the use of vasopressor therapy
  • Ventilator free days [ Time Frame: 28 days after admission ]
    The number of calendar days between admission and 28 days later that the patients is alive and without the use of mechanical ventilation. Ventilator meaning mechanical ventilation via endotracheal or tracheostomy tube, except those intubated solely for a procedure. Non-invasive mechanical ventilation will not be included.
  • Renal replacement free days [ Time Frame: 28 days after admission ]
    The number of calendar days between admission and 28 days later that the patient is alive and without renal replacement therapy. Patients with chronic renal replacement therapy initiated prior to the current admission will not be included unless worsen.
  • Serious adverse reactions [ Time Frame: 4 days after randomization ]
    Number of serious adverse reactions (SARs) in the 2 arms. SARs is defined as any untoward medical reactions that at any dose results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalization, results in persistent or significant disability or incapacity or is a congenital anomaly or birth defect.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2019)
  • Mortality [ Time Frame: Until day 90 ]
    All-cause mortality at day 28 and 90.
  • Hospital length of stay [ Time Frame: Day 90 ]
    Number of days admitted to the hospital
  • Use of vasopressor [ Time Frame: Until day 28 ]
    Number of vasopressor-free days
  • Use of ventilator [ Time Frame: Until day 28 ]
    Number of ventilator-free days
  • Need for renal replacement [ Time Frame: Until day 28 ]
    Number of renal replacement free days
  • Serious adverse reactions [ Time Frame: Until day 4 ]
    Number of SAR in the 2 arms
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Infusion of Prostacyclin vs Placebo for 72-hours in Trauma Patients With Haemorrhagic Shock Suffering From Organ Failure
Official Title  ICMJE Efficacy and Safety of 72-hour Infusion of Prostacyclin (1 Nanogram(ng)/Kilogram(kg)/Minute(Min)) in Trauma Patients With Haemorrhagic Shock Induced Endotheliopathy.
Brief Summary

A multicenter, randomized (1:1, iloprost: placebo), placebo controlled, blinded, investigator-initiated phase 2b trial in trauma patients with haemorrhagic shock and shock induced endotheliopathy (SHINE), investigating the efficacy and safety of continuous intravenous administrating of iloprost (1 ng/kg/min) versus placebo for 72-hours, in a total of 220 patients.

The study hypothesis is that iloprost may be beneficial as an endothelial rescue treatment as it is anticipated to deactivate the endothelium and restore vascular integrity in trauma patients with haemorrhagic shock (SHINE) suffering from organ failure caused by endothelial breakdown, ultimately improving survival.

Detailed Description

The main objective in this trial is to investigate whether continuous infusion of iloprost at a dose of 1 ng/kg/min for 72-hours is safe and significantly increase the number of intensive care unit (ICU) free days, within 28 days from admission compared to infusion of placebo in trauma patients with haemorrhagic shock and SHINE.

Patients are presented at the investigator site in an acute critical condition and therefore informed consent will be obtained from a scientific guardian. Next-of-kin and subsequently the patient will co-sign as soon as possible. During the trial additional blood samples will be obtained daily for the first 72 hours. Patients will be observed and assessed continuously. During the extended follow up period at day 28 and 90, no contact will be made to the patient, but the data will be collected from department/hospital databases to establish length of stay and potential mortality.

The trial is conducted in accordance with the Helsinki 2 declaration and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Guideline for Good Clinical Practice (ICH-GCP) and in compliance with the protocol. As part of the quality assurance site monitoring will be performed by an independent GCP-Unit including source data verification. Standard Operation Procedure to address protocol specific procedures such as data collection and adverse event reporting are developed.

The power calculation is based on not yet published data from the following trial 'Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (iTACTIC)' [NTC 02593877] having the same in- and exclusion criteria as the present trial. The number of ICU free days within 30-days from admission is chosen as the primary endpoint and a clinically relevant increase in ICU free days within 28-days of 30% with α 0.05, power 0.85 will require 107 patients in each 1:1 randomization group. We plan on including 110 patients in each group and 220 in total. The final statistical analysis plan will be published before the last patient is included in the trial and analysis of the data from the randomized trial will be performed by Theis Lange, Associate Professor, Section of Biostatistics, Department of Public Health, University of Copenhagen.

The primary end point will be analyzed using linear regression adjusted for site. Effect size will be summarized using adjusted mean differences with confidence intervals based on robust standard errors as residuals are not expected to be normally distributed. The same analysis will be employed to continuous secondary outcomes. All-cause mortality will be further illustrated using Kaplan-Meier curves. All analysis will be conducted following the intention to treat principle (this will be the primary analysis) and per-protocol. In addition, the following patient subgroup will also be analyzed separately:

• Patients with traumatic brain injury

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Both patient, investigator and outcome assessor will be blinded
Primary Purpose: Treatment
Condition  ICMJE Multi Organ Failure
Intervention  ICMJE
  • Drug: Iloprost
    continuously infusion for 72 hours 1 ng/kg/min
    Other Name: Intervention
  • Drug: Isotonic saline
    continuously infusion for 72 hours equal volume to Iloprost
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: Iloprost
    Patients randomized to active treatment (n = 110 patients) will receive continuous infusion of iloprost for 72 hours after inclusion or until discharge to ward or death, whichever comes first
    Intervention: Drug: Iloprost
  • Placebo Comparator: Placebo
    Patients randomized to placebo treatment (n= 110 patients) will receive continuous infusion of isotonic saline (equal volume) for 72 hours after inclusion or until discharge to ward or death, whichever comes first.
    Intervention: Drug: Isotonic saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 3, 2019)
220
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 30, 2021
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18 years
  • Present with clinical signs of hemorrhagic shock (defined by systolic blood pressure <90 millimetre of mercury (mmHg) or use of pre-hospital blood transfusion).
  • Activation of local massive transfusion protocol and initiation of the first transfusion after admission.
  • Randomised within 5 hours of injury and 3 hours of admission to the emergency department of the participating trial site.
  • Consent is provided on behalf of incapacitated patients by Scientific Guardian

Exclusion Criteria:

  • Withdrawal from active therapy
  • Known hypersensitivity to Iloprost.
  • Pregnancy (non-pregnancy confirmed by patient having a negative urine or plasma choriogonadotropin (hCG) or being postmenopausal defined as females at 60 years old and beyond)
  • Known severe heart failure (New York Heart Association (NYHA) class IV)
  • Suspected acute coronary syndrome
  • Estimated weight < 40 kg
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pär I Johansson, MD, MPA +45 3545 2032 per.johansson@regionh.dk
Contact: Jakob Stensballe, MD, PhD +45 3545 8587 Jakob.Stensballe@regionh.dk
Listed Location Countries  ICMJE Denmark,   Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03903939
Other Study ID Numbers  ICMJE SHINE-TRAUMA
2019-000936-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Pär Johansson, Rigshospitalet, Denmark
Study Sponsor  ICMJE Pär Johansson
Collaborators  ICMJE
  • Odense University Hospital
  • Aarhus University Hospital
  • Aalborg University Hospital
  • Oslo University Hospital
Investigators  ICMJE
Study Director: Pär I Johansson, MD, MPA University of Copenhagen (Rigshospitalet)
PRS Account Rigshospitalet, Denmark
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP