Multi Organ FailurePhase 2SHINE-TRAUMANCT03903939
Infusion of Prostacyclin vs Placebo for 72-hours in Trauma Patients With Haemorrhagic Shock Suffering From Organ Failure
A Phase 2 study testing Iloprost and Isotonic saline in people with Multi Organ Failure, run by Pär Johansson at 5 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multi Organ Failure
- What is being tested?
- Iloprost and Isotonic saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 228 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 22 May 2019to 14 Nov 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Denmark4 sites
Aalborg University Hospital
Aalborg, 9100
Aarhus University Hospital
Aarhus, 8200
Rigshospitalet (University of Copenhagen)
Copenhagen
Odense University Hospital
Odense, 5000
About this study
Official title: Efficacy and Safety of 72-hour Infusion of Prostacyclin (1 Nanogram(ng)/Kilogram(kg)/Minute(Min)) in Trauma Patients With Haemorrhagic Shock Induced Endotheliopathy.
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.
Read the 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
- Conditions
- Multi Organ Failure
- Being tested
- Iloprost, Isotonic saline
- Keywords
- Trauma patients, Shock-induced endotheliopathy
- Medical subject headings
- Multiple Organ Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IloprostDrug
Also called Intervention
continuously infusion for 72 hours 1 ng/kg/min
Isotonic salineDrug
Also called Placebo
continuously infusion for 72 hours equal volume to Iloprost
| Study group | Role | What they receive |
|---|---|---|
| Iloprost | Experimental | 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 Receives: Drug: Iloprost |
| Placebo | Placebo comparator | 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. Receives: Drug: Isotonic saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days after admission
Secondary outcomes (6)
All-cause mortality
Vital status of the patient at day 28 and 90.
Measured: 90 days after admission
Hospital length of stay
Defined as the total number of days admitted to the hospital until day 90
Measured: 90 days after admission
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
Measured: 28 days after admission
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.
Measured: 28 days after admission
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.
Measured: 28 days after admission
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.
Measured: 4 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2019
- Study start22 May 2019
- Primary completion14 Nov 2021
- Study completion14 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multi Organ FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 228 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pär Johansson
- Sponsor type
- University, hospital or other
- Collaborators
- Odense University Hospital, Aarhus University Hospital, Aalborg University Hospital, Oslo University Hospital
- Responsible party
- Sponsor-investigator, Pär Johansson, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Pär I Johansson, MD, MPA, Study director, University of Copenhagen (Rigshospitalet)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03903939
- Sponsor's protocol ID
- SHINE-TRAUMA
- Other IDs
- 2019-000936-24, 2019
- Acronym
- SHINE-TRAUMA
- Status last verified
- May 2024
- First submitted
- 3 Apr 2019
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Johansson PI, Eriksen CF, Schmal H, Gaarder C, Pall M, Henriksen HH, Bovbjerg P, Lange T, Naess PA, Nielsen C, Kirkegaard H, Stensballe J. Efficacy and safety of iloprost in trauma patients with haemorrhagic shock-induced endotheliopathy-Protocol for the multicentre randomized, placebo-controlled, blinded, investigator-initiated shine-trauma trial. Acta Anaesthesiol Scand. 2021 Apr;65(4):551-557. doi: 10.1111/aas.13776. Epub 2021 Jan 11.
PubMed 33393084
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of 72-hour Infusion of Prostacyclin (1 Nanogram(ng)/Kilogram(kg)/Minute(Min)) in Trauma Patients With Haemorrhagic Shock Induced Endotheliopathy.
- ClinicalTrials.gov ID
- NCT03903939
- Acronym / sponsor ID
- SHINE-TRAUMA / SHINE-TRAUMA
- Conditions
- Multi Organ Failure
- Keywords
- Trauma patients, Shock-induced endotheliopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 228 participants (actual)
- Lead sponsor
- Pär JohanssonUniversity, hospital or other
- Collaborators
- Odense University Hospital, Aarhus University Hospital, Aalborg University Hospital, Oslo University Hospital
- Study start
- 22 May 2019 (actual)
- Primary completion
- 14 Nov 2021 (actual)
- Study completion
- 14 Nov 2021 (actual)
- First posted
- 4 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Iloprost | Experimental | Drug: IloprostPatients 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 |
| Placebo | Placebo comparator | Drug: Isotonic salinePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IloprostAlso: Interventioncontinuously infusion for 72 hours 1 ng/kg/min | Drug | Iloprost |
| Isotonic salineAlso: Placebocontinuously infusion for 72 hours equal volume to Iloprost | Drug | Placebo |
Primary outcome
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
6 secondary outcomes
All-cause mortality
Time frame: 90 days after admission
Hospital length of stay
Time frame: 90 days after admission
Vasopressor free days
Time frame: 28 days after admission
Ventilator free days
Time frame: 28 days after admission
Renal replacement free days
Time frame: 28 days after admission
Serious adverse reactions
Time frame: 4 days after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Derived from this study: PubMed 33393084Johansson PI, Eriksen CF, Schmal H, Gaarder C, Pall M, Henriksen HH, Bovbjerg P, Lange T, Naess PA, Nielsen C, Kirkegaard H, Stensballe J. Efficacy and safety of iloprost in trauma patients with haemorrhagic shock-induced endotheliopathy-Protocol for the multicentre randomized, placebo-controlled, blinded, investigator-initiated shine-trauma trial. Acta Anaesthesiol Scand. 2021 Apr;65(4):551-557. doi: 10.1111/aas.13776. Epub 2021 Jan 11.
- Publication of resultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pär I Johansson, MD, MPA study director
University of Copenhagen (Rigshospitalet)
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Iloprost and Isotonic saline in people with Multi Organ Failure, run by Pär Johansson at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Denmark, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ICU free days (time frame: 28 days after admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03903939, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.