Co-administration of Iloprost and Eptifibatide in Septic Shock Patients

Inclusion criteria

• 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
• 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

Exclusion criteria

• 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
• 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