Septic ShockPhase 2CO-ILEPSSNCT02204852
Co-administration of Iloprost and Eptifibatide in Septic Shock Patients
A Phase 2 study testing Iloprost+eptifibatide in people with Septic Shock, run by Sisse R. Ostrowski, MD PhD DMSc at 1 site in Denmark.
Trial summary
Objective Evaluating the safety and efficacy of iloprost and eptifibatide co-administration compared to placebo as an addition to standard care in septic shock patients. Trial rationale Iloprost and eptifibatide combination therapy in septic shock patients is expected to deactivate the endothelium and restore vascular… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Septic Shock
- What is being tested?
- Iloprost+eptifibatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteDenmark
- Study dates
- Sep 2014to Aug 2016
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult intensive care patients (age ≥18 years) AND
- Sepsis, defined as suspected or confirmed site of infection or positive blood culture and ≥2 of 4 systemic inflammatory response syndrome (SIRS) criteria fulfilled within the last 24h:
- Temperature ≤ 36˚ C or ≥ 38˚C
- Heart rate ≥ 90 beats per minute
- Mechanical ventilation for acute respiratory process or respiratory rate ≥ 20 breaths per minute or PaCO2 < 4.2 kPa
- WBC ≥ 12,000/mm³ OR ≤ 4,000/mm³ OR > 10% bands AND
Show all 12Show fewer
- Septic shock within the last 24h, defined as:
- Hypotension (MAP <70 mmHg, Lactate 4 mmol/L) despite ongoing resuscitation with fluids (crystalloids, colloids, blood products) within the last 24h OR
- ≥30 ml/kg ideal body weight (IBW) fluid (crystalloids, colloids, blood products) given in the last 24h AND
- Need for vasopressor/inotropic agents (noradrenaline, adrenaline, dopamine) within the last 24h AND
- Can be randomized into trial and dosed < 24h after septic shock diagnosis (the time-point for the septic shock diagnosis corresponds to the time-point where the vasopressor/inotropic therapy (3c) is initiated) AND
- Consent is obtainable
Who cannot join
- Patient is pregnant or breast-feeding
- Patient weights more than 125 kg
- Patients with known allergy towards any of the investigational products or contraindications which should be excluded according to the investigational product specifications
- Patients in whom the clinician finds antithrombotic therapy contraindicated - prophylaxis included
- Patients at increased risk of bleeding:
- Surgery in the previous 48h and expected surgery within 48 h
Show all 32Show fewer
- Epidural or spinal puncture in the previous 12h
- Platelet count less than 10,000/mm3 in the previous 24h
- Need of blood products for bleeding in the previous 24h (3 or more RBC/24 h)
- Treatment with any antithrombotics within 12h (profylaxis excepted)
- Current intracranial bleeding
- Traumatic brain or spinal injury within the last month
- Patients requiring any form of antithrombotics (beyond profylaxis) in therapeutic doses or prothrombotics in any dose, including:
- Unfractionated heparin within 8h before the infusion (prophylactic heparin up to 15,000 U/day permitted)
- LMWH within 12h before the infusion (prophylactic doses permitted)
- Warfarin within 1 day before the infusion
- Acetylsalicylic acid more than 650 mg/day within 3 days before the study
- Thrombolytic therapy within 3 days before the study (catheter clearance doses permitted)
- GPIIb/IIIa receptor inhibitors within 4 days before the study
- Antithrombin III with dose greater than 10,000 U within 12h before the study
- Patients with a do-not-resuscitate order (expected not to survive more than few days because of uncorrectable medical or surgical condition other than sepsis)
- Patient with chronic renal failure requiring dialysis (renal failure without need for dialysis permitted)
- Patients who have undergone transplantation of bone marrow, liver, pancreas, heart, lung, or bowel (kidney transplant permitted)
- Patient with known hypercoagulable condition:
- Activated protein C resistance
- Hereditary protein C, protein S, or antithrombin III deficiency
- Anticardiolipin or antiphospholipid antibody
- Lupus anticoagulant
- Homocysteinemia
- Recent or highly suspected pulmonary embolism or deep venous thrombosis (within 3 months)
- Patients with known congenital hypocoagulable diseases
- Patient with known primary pulmonary hypertension
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Anesthesia and Intensive Care, Nordsjællands Hospital
Hillerød, Capital Region, DK-3400
About this study
Official title: Safety and Efficacy of Iloprost and Eptifibatide Co-administration Compared to Standard Therapy in Patients With Septic Shock - a Randomized, Controlled, Double-blind Investigator-initiated Trial
Objective Evaluating the safety and efficacy of iloprost and eptifibatide co-administration compared to placebo as an addition to standard care in septic shock patients.
Trial rationale Iloprost and eptifibatide combination therapy in septic shock patients is expected to deactivate the endothelium and restore vascular integrity, reduce formation of microvascular thrombosis and dissolve existing clots in the microcirculation and maintain platelet counts, thereby improving platelet-mediated immune function and reducing the risk of bleeding. Together this is expected to translate into reduced organ failure and improved outcome in patients with septic shock.
Read more
Trial population The trial population is patients >18 years admitted to the ICU with septic shock within the last 24h. Eighteen evaluable septic shock patients will be included.
Trial design This is a single center, randomized (2:1, active:placebo), placebo controlled, double-blind investigator-initiated phase IIa trial in patients with septic shock, investigating the safety and efficacy of co-administration of Iloprost and Eptifibatide as a 48h continuous i.v infusion in totally 18 patients.
All patients will receive standard ICU care including LMWH thrombosis prophylaxis.
As all patients present at the trial site in an acute, critical condition, scientific guardians will co-sign the informed consent form before inclusion. Next-of-kin and the patients' general practitioner will co-sign as soon as possible and the patient will provide informed consent whenever possible. The active treatment is expected to improve the clinical condition of the individual patient and to provide information that may translate into improved therapy of future sepsis patients.
During the study, blood samples will be taken at different time points. Patients will be observed and assessed continuously with regards to complications including bleeding. Patients will be actively assessed as long as the patient is in the ICU. During the extended follow up period at day 30 and 90, contact will be made with the patients to follow up on safety events and vital status.
The trial is conducted in accordance with the protocol and the current regulatory requirements and legislation in Denmark.
Investigational product The active treatment in the trial comprises co-administration of 1 ng/kg/min Ilomedin® and 0.5 µg/kg/min Integrilin® as 48h continuous i.v infusions. The drugs will be purchased and administered according to the product specifications.
Placebo The placebo in the trial is 0.9% saline as 48h continuous i.v infusion, which will be used as placebo for both study drugs. The i.v volume of placebo saline to be administered is equal to the administered volume of diluted (in 0.9% saline) active drug.
Data protection In compliance with the Danish data protection law, the trial will be approved by the Danish Data Protection Agency.
Sponsor of study and financial support This research project is investigator-initiated by the trial sponsor and co-investigator Sisse R. Ostrowski and co-investigator Pär I. Johansson in collaboration with the principal investigator Morten Bestle.
It has not received funding from any commercial sponsors.
Time line Patient recruitment period runs from September 2014 to August 2015. Follow-up data on 30-day and 90-day outcome and adverse events will be collected. Initial data analyses will be done after completion of 30-day follow-up for all patients. Secondary data analyses will be done after completion of 90-day follow-up for all patients.
- Conditions
- Septic Shock
- Being tested
- Iloprost+eptifibatide, Placebo
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iloprost+eptifibatideDrug
Also called Ilomedin(R), Integrilin(R)
PlaceboDrug
Also called 0.9% saline, double dummy
| Study group | Role | What they receive |
|---|---|---|
| Iloprost+eptifibatide | Experimental | Co-administration of 1 ng/kg/min Ilomedin® and 0.5 µg/kg/min Integrilin® as 48h continuous i.v infusions Receives: Drug: Iloprost+eptifibatide |
| Saline | Placebo comparator | Double dummy 0.9% saline as 48h continuous i.v infusion Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change i plasma biomarkers reflecting endothelial damage
Change in biomarkers indicative of endothelial activation and damage (sE-selectin, syndecan-1, thrombomodulin, sVE-cadherin, nucleosomes) from baseline to 48 hours post-randomization
Measured: 48 hours
Mean change in platelet count reflecting platelet consumption
Change in platelet count from baseline to 48 hours post-randomization
Measured: 48 hours
Mean change in biomarkers reflecting fibrinolysis
Change in D-dimer and fibrin split products indicative of fibrinolysis (fibrinogen degradation Bβ15-42; fibrin degradation Fragments X, Y, D and E) from baseline to 48 hours post-randomization
Measured: 48 hours
Secondary outcomes (5)
Number of patients with severe bleeding
Severe bleeding (intracranial or clinical bleeding with the use of 3 RBC units or more/24 hours)
Measured: 24 hours to 90 days
Number of patients with transfusion requirements
Use of blood products (in ICU) post-randomization
Measured: 24 hours to 90 days
Mortality
Difference in day 7, 30 and 90 day mortality between patients receiving active treatment (eptifibatide and iloprost) and placebo
Measured: 7 to 90 days
Mean change in disease severity score
Changes in SOFA score from baseline to 48 h and day 5 and 7 post-randomization
Measured: 48 hours to 7 days
Number of patients requiring organ support
Days of vasopressor, ventilator and renal replacement therapy post-randomization
Measured: 48 hours to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2014 (estimated)
- Study startSep 2014
- Primary completionAug 2016
- Study completionAug 2016
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 Septic ShockStudies 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
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sisse R. Ostrowski, MD PhD DMSc
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sisse R. Ostrowski, MD PhD DMSc, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Sisse R Ostrowski, MD, PhD, DMSc, Study chair, Copenhagen University Hospital, Rigshospitalet, DenmarkPär I Johansson, MD, DMSc, MPA, Study director, Copenhagen University Hospital, Rigshospitalet, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02204852
- Sponsor's protocol ID
- CO-ILEPSS
- Acronym
- CO-ILEPSS
- Status last verified
- Apr 2017
- First submitted
- 24 Jul 2014
- Last updated
- 24 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Berthelsen RE, Ostrowski SR, Bestle MH, Johansson PI. Co-administration of iloprost and eptifibatide in septic shock (CO-ILEPSS)-a randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacy. Crit Care. 2019 Sep 5;23(1):301. doi: 10.1186/s13054-019-2573-8.
PubMed 31488213
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Iloprost and Eptifibatide Co-administration Compared to Standard Therapy in Patients With Septic Shock - a Randomized, Controlled, Double-blind Investigator-initiated Trial
- ClinicalTrials.gov ID
- NCT02204852
- Acronym / sponsor ID
- CO-ILEPSS / CO-ILEPSS
- Conditions
- Septic Shock
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Sisse R. Ostrowski, MD PhD DMScUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 30 Jul 2014 (estimated)
- 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.
Objective Evaluating the safety and efficacy of iloprost and eptifibatide co-administration compared to placebo as an addition to standard care in septic shock patients.
Trial rationale Iloprost and eptifibatide combination therapy in septic shock patients is expected to deactivate the endothelium and restore vascular integrity, reduce formation of microvascular thrombosis and dissolve existing clots in the microcirculation and maintain platelet counts, thereby improving platelet-mediated immune function and reducing the risk of bleeding. Together this is expected to translate into reduced organ failure and improved outcome in patients with septic shock.
Trial population The trial population is patients >18 years admitted to the ICU with septic shock within the last 24h. Eighteen evaluable septic shock patients will be included.
Trial design This is a single center, randomized (2:1, active:placebo), placebo controlled, double-blind investigator-initiated phase IIa trial in patients with septic shock, investigating the safety and efficacy of co-administration of Iloprost and Eptifibatide as a 48h continuous i.v infusion in totally 18 patients.
All patients will receive standard ICU care including LMWH thrombosis prophylaxis.
As all patients present at the trial site in an acute, critical condition, scientific guardians will co-sign the informed consent form before inclusion. Next-of-kin and the patients' general practitioner will co-sign as soon as possible and the patient will provide informed consent whenever possible. The active treatment is expected to improve the clinical condition of the individual patient and to provide information that may translate into improved therapy of future sepsis patients.
During the study, blood samples will be taken at different time points. Patients will be observed and assessed continuously with regards to complications including bleeding. Patients will be actively assessed as long as the patient is in the ICU. During the extended follow up period at day 30 and 90, contact will be made with the patients to follow up on safety events and vital status.
The trial is conducted in accordance with the protocol and the current regulatory requirements and legislation in Denmark.
Investigational product The active treatment in the trial comprises co-administration of 1 ng/kg/min Ilomedin® and 0.5 µg/kg/min Integrilin® as 48h continuous i.v infusions. The drugs will be purchased and administered according to the product specifications.
Placebo The placebo in the trial is 0.9% saline as 48h continuous i.v infusion, which will be used as placebo for both study drugs. The i.v volume of placebo saline to be administered is equal to the administered volume of diluted (in 0.9% saline) active drug.
Data protection In compliance with the Danish data protection law, the trial will be approved by the Danish Data Protection Agency.
Sponsor of study and financial support This research project is investigator-initiated by the trial sponsor and co-investigator Sisse R. Ostrowski and co-investigator Pär I. Johansson in collaboration with the principal investigator Morten Bestle.
It has not received funding from any commercial sponsors.
Time line Patient recruitment period runs from September 2014 to August 2015. Follow-up data on 30-day and 90-day outcome and adverse events will be collected. Initial data analyses will be done after completion of 30-day follow-up for all patients. Secondary data analyses will be done after completion of 90-day follow-up for all patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Iloprost+eptifibatide | Experimental | Drug: Iloprost+eptifibatideCo-administration of 1 ng/kg/min Ilomedin® and 0.5 µg/kg/min Integrilin® as 48h continuous i.v infusions |
| Saline | Placebo comparator | Drug: PlaceboDouble dummy 0.9% saline as 48h continuous i.v infusion |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Adult intensive care patients (age ≥18 years) AND
- Sepsis, defined as suspected or confirmed site of infection or positive blood culture and ≥2 of 4 systemic inflammatory response syndrome (SIRS) criteria fulfilled within the last 24h:
- Septic shock within the last 24h, defined as:
- Can be randomized into trial and dosed < 24h after septic shock diagnosis (the time-point for the septic shock diagnosis corresponds to the time-point where the vasopressor/inotropic therapy (3c) is initiated) AND
- Consent is obtainable
Key exclusion criteria (32 listed)
- Patient is pregnant or breast-feeding
- Patient weights more than 125 kg
- Patients with known allergy towards any of the investigational products or contraindications which should be excluded according to the investigational product specifications
- Patients in whom the clinician finds antithrombotic therapy contraindicated - prophylaxis included
- Patients at increased risk of bleeding:
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 |
|---|---|---|
| Iloprost+eptifibatideAlso: Ilomedin(R), Integrilin(R) | Drug | Iloprost+eptifibatide |
| PlaceboAlso: 0.9% saline, double dummy | Drug | Saline |
Primary outcome
Mean change i plasma biomarkers reflecting endothelial damage
Time frame: 48 hours
Change in biomarkers indicative of endothelial activation and damage (sE-selectin, syndecan-1, thrombomodulin, sVE-cadherin, nucleosomes) from baseline to 48 hours post-randomization
Mean change in platelet count reflecting platelet consumption
Time frame: 48 hours
Change in platelet count from baseline to 48 hours post-randomization
Mean change in biomarkers reflecting fibrinolysis
Time frame: 48 hours
Change in D-dimer and fibrin split products indicative of fibrinolysis (fibrinogen degradation Bβ15-42; fibrin degradation Fragments X, Y, D and E) from baseline to 48 hours post-randomization
5 secondary outcomes
Number of patients with severe bleeding
Time frame: 24 hours to 90 days
Number of patients with transfusion requirements
Time frame: 24 hours to 90 days
Mortality
Time frame: 7 to 90 days
Mean change in disease severity score
Time frame: 48 hours to 7 days
Number of patients requiring organ support
Time frame: 48 hours to 90 days
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 24 Apr 2017.
- Derived from this study: PubMed 31488213Berthelsen RE, Ostrowski SR, Bestle MH, Johansson PI. Co-administration of iloprost and eptifibatide in septic shock (CO-ILEPSS)-a randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacy. Crit Care. 2019 Sep 5;23(1):301. doi: 10.1186/s13054-019-2573-8.
Related trials for Septic Shock
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
Not yet recruitingObservational study
Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
Sepsis, Septic Shock Hyperdynamic
RecruitingObservational study
Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Sepsis
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.
Sisse R Ostrowski, MD, PhD, DMSc study chair
Copenhagen University Hospital, Rigshospitalet, Denmark
Pär I Johansson, MD, DMSc, MPA study director
Copenhagen University Hospital, Rigshospitalet, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Iloprost+eptifibatide in people with Septic Shock, run by Sisse R. Ostrowski, MD PhD DMSc at 1 site in Denmark.
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 12 inclusion and 32 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 24 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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?
Mean change i plasma biomarkers reflecting endothelial damage (time frame: 48 hours). The study lists 3 primary outcomes in all. 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 NCT02204852, 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 24 Apr 2017.