A

Phase 1

Conditions: Septic shock
MedDRA version: 17.0Level: PTClassification code 10040070Term: Septic shockSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2014-002440-41-DK

Lead Sponsor: Rigshospitalet, Capital Region Bloodbank 2034, Section for Transfusion Medicine

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

1. Adult intensive care patients (age =18 years)
AND
2. 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:
a) Temperature = 36° C or = 38°C
b) Heart rate = 90 beats per minute
c) Mechanical ventilation for acute respiratory process or respiratory rate = 20 breaths per min or PaCO2 < 4.2kPa
d) WBC = 12,000/mm³ OR = 4,000/mm³ OR > 10% bands
AND
3. Septic shock within the last 24h, defined as:
a. Hypotension (MAP <70 mmHg, Lactate 4 mmol/L) despite ongoing resuscitation with fluids (crystalloids, colloids, blood products) within the last 24h OR
b. =30 ml/kg ideal body weight (IBW) fluid (crystalloids, colloids, blood products) given in the last 24h AND
c. Need for vasopressor/inotropic agents (noradrenaline, adrenaline, dopamine) within the last 24h
AND
4. Can be randomized into trial and dosed < 24 hours 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
5. Consent is obtainable
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion Criteria

1. Patient is pregnant or breast-feeding
2. Patient weights more than 125 kg
3. Patients with known allergy towards any of the investigational products or contraindications which
should be excluded according to the investigational product specifications
4. Patients in whom the clinician finds antithrombotic therapy contraindicated - prophylaxis included
5. Patients at increased risk of bleeding:
a. Surgery in the previous 48 hours and expected surgery within 48 hours
b. Epidural or spinal puncture in the previous 12 hours
c. Platelet count less than 10,000/mm3 in the previous 24 hours
d. Need of blood products for bleeding in the previous 24 hours (3 or more RBC/24 h)
e. Treatment with any antithrombotics within 12 hours (profylaxis excepted)
f. Current intracranial bleeding
g. Traumatic brain or spinal injury within the last month
6. Patients requiring any form of antithrombotics (beyond profylaxis) in therapeutic doses or
prothrombotics in any dose, including:
a. Unfractionated heparin within 8 hours before the infusion (prophylactic heparin up to 15,000 U/day permitted)
b. LMWH within 12 hours before the infusion (prophylactic doses permitted)
c. Warfarin within 1 day before the infusion
d. Acetylsalicylic acid more than 650 mg/day within 3 days before the study
e. Thrombolytic therapy within 3 days before the study (catheter clearance doses permitted)
f. GPIIb/IIIa receptor inhibitors within 4 days before the study
g. Antithrombin III with dose greater than 10,000 U within 12 hours before the study
7. 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)
8. Patient with chronic renal failure requiring dialysis (renal failure without need for dialysis permitted)
9. Patients who have undergone transplantation of bone marrow, liver, pancreas, heart, lung, or bowel (kidney transplant permitted)
10. Patient with known hypercoagulable condition:
a. Activated protein C resistance
b. Hereditary protein C, protein S, or antithrombin III deficiency
c. Anticardiolipin or antiphospholipid antibody
d. Lupus anticoagulant
e. Homocysteinemia
f. Recent or highly suspected pulmonary embolism or deep venous thrombosis (within 3 months)
11. Patients with known congenital hypocoagulable diseases
12. Patient with known primary pulmonary hypertension

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main 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. ;Secondary Objective: NA;Primary end point(s): * Change in biomarkers indicative of endothelial activation and damage from baseline to 48 hours post-randomization <br>* Change in platelet count from baseline to 48 hours post-randomization <br>* Change in D-dimer and fibrin split products indicative of fibrinolysis from baseline to 48 hours post-randomization ;Timepoint(s) of evaluation of this end point: 48 hours post-randomization

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): * Severe bleeding (intracranial or clinical bleeding with the use of 3 RBC units or more/24 hours) <br>* Use of blood products (in ICU) post-randomization <br>* Difference in day 7, 30 and 90 day mortality between patients receiving active treatment and placebo <br>* Changes in SOFA score from baseline to 48 h and day 5 and 7 post-randomization <br>* Days of vasopressor, ventilator and renal replacement therapy post-randomization ;Timepoint(s) of evaluation of this end point: The secondary endpoint are evaluated througout the 48 hour treatment period and after 7, 30 and 90 days