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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03903939
Other study ID # SHINE-TRAUMA
Secondary ID 2019-000936-24
Status Completed
Phase Phase 2
First received
Last updated
Start date May 22, 2019
Est. completion date November 14, 2021

Study information

Verified date May 2024
Source Rigshospitalet, Denmark
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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


Recruitment information / eligibility

Status Completed
Enrollment 228
Est. completion date November 14, 2021
Est. primary completion date November 14, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
Iloprost
continuously infusion for 72 hours 1 ng/kg/min
Isotonic saline
continuously infusion for 72 hours equal volume to Iloprost

Locations

Country Name City State
Denmark Aalborg University Hospital Aalborg
Denmark Aarhus University Hospital Aarhus
Denmark Rigshospitalet (University of Copenhagen) Copenhagen
Denmark Odense University Hospital Odense
Norway Oslo University Hospital Oslo

Sponsors (5)

Lead Sponsor Collaborator
Pär Johansson Aalborg University Hospital, Aarhus University Hospital, Odense University Hospital, Oslo University Hospital

Countries where clinical trial is conducted

Denmark,  Norway, 

Outcome

Type Measure Description Time frame Safety issue
Primary ICU free days 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 28 days after admission
Secondary All-cause mortality Vital status of the patient at day 28 and 90. 90 days after admission
Secondary Hospital length of stay Defined as the total number of days admitted to the hospital until day 90 90 days after admission
Secondary Vasopressor free days The number of calendar days between admission and 28 days later that the patients is alive and without the use of vasopressor therapy 28 days after admission
Secondary Ventilator free days 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. 28 days after admission
Secondary Renal replacement free days 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. 28 days after admission
Secondary Serious adverse reactions 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. 4 days after randomization
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