NCT02204852: CO-ILEPSS

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

Completed Phase 2 Last updated 21 April 2017

What this trial tests

Phase 2 trial testing Iloprost+eptifibatide in Septic Shock in 18 participants. Completed in 1 August 2016.

Timeline

1 September 2014

Primary endpoint
1 August 2016

1 August 2016

Quick facts

Lead sponsor	Sisse R. Ostrowski, MD PhD DMSc
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	single group
Masking	quadruple
Primary purpose	treatment
Enrollment	18
Start date	1 September 2014
Primary completion	1 August 2016
Estimated completion	1 August 2016
Sites	1 location across Denmark

Drugs / interventions tested

• Iloprost+eptifibatide — full drug profile →
• Placebo

Conditions studied

• Septic Shock — all drugs for Septic Shock →

Sponsor

Sisse R. Ostrowski, MD PhD DMSc — full company profile →

Who can join

Adults 18 to 99, any sex, with Septic Shock. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immune therapy in sepsis: Are we ready to try again?
   Davies R, O'Dea K, Gordon A. · · 2018 · cited 52× · PMID 30515242 · DOI 10.1177/1751143718765407
2. Endothelial Activation and Microcirculatory Disorders in Sepsis.
   Raia L, Zafrani L. · · 2022 · cited 34× · PMID 35721048 · DOI 10.3389/fmed.2022.907992
3. Co-administration of iloprost and eptifibatide in septic shock (CO-ILEPSS)-a randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacy.
   Berthelsen RE, Ostrowski SR, Bestle MH, Johansson PI. · · 2019 · cited 26× · PMID 31488213 · DOI 10.1186/s13054-019-2573-8