Treatment with Iloprost and Integrilin compared to standard care in severe pneumonia patients with severe sepsis.

Phase 1

Conditions: Severe pneumonia with Sepsis and Septic Shock
MedDRA version: 16.0Level: PTClassification code 10040070Term: Septic shockSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2011-002254-31-DK

Lead Sponsor: Rigshospitalet, ITA 4131, Department of Intensive care

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 36

Inclusion Criteria

1. At least 18 years of age AND

2. Suspected or proven bacterial pneumonia requiring administration of antibiotics:
•Clinical diagnosis of pneumonia, (i.e. new or increased cough, production of purulent sputum or a change in the character of sputum in subjects who normally have purulent sputum, typical auscultatory findings of pneumonia on chest examination) and:

•chest radiograph or CT within the last 24 hr showing a pulmonary infiltrate

3. Dyspnea and/or tachypnea (>20 breaths/minute) or mechanical ventilation

4. Two or more systemic inflammatory response syndrome (SIRS) criteria within the last 24 hours:

-Temperature /= 38°C
-Heart rate >/= 90 beats per minute
-Mechanical ventilation for acute respiratory process or respiratory rate >/= 20 breaths per minute or PaC02 < 4.2 kPa
-WBC >/= 12,000/mm³ OR 10% bands

5. At least one organ failure beyond respiratory failure (cerebral, cardiovascular, hepatic, renal or coagulation within the last 24 hours (> 2 in SOFA score for the specific organ system) AND

6. Can be randomized into trial and dosed < 48 h after severe sepsis diagnosis AND

7. 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 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

Exclusion Criteria

1. Patient is pregnant or breast-feeding

2. Patient weigh 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. Investigators clinical decision deeming study participation not favourable for the patient

5. Patients in whom the clinician finds antithrombotic therapy contraindicated – prophylaxis included

6. Patients at increased risk of bleeding: Surgery in the previous 6 h, expected surgery within 72 h, epidural or spinal puncture in the previous 12 h, platelet count less than 20,000/mm3 or TEG MA<40 mm in the previous 24 h, INR > 2; if available TEG should be measured and the patient will only be excluded if the R-time is >10 min, need of blood products for bleeding in the previous 6 h, treatment with any antithrombotics within 12 h (profylaxis excepted), current or previous intracranial bleeding or traumatic brain or spinal injury within the last month.

7. 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.Low-molecular-weight heparin at inclusion(prophylactic doses permitted). If TEG analysis is available the patient will only be excluded if the R-time > 10 min.
c.Having received Warfarin and TEG R>10 min at inclusion
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.Glycoprotein IIb-IIIa antagonists within 3 days before the study.
g.Antithrombin III with dose greater than 10,000 U within 12 hours before the study.
h.Protein C within 24 hours of the study.
8. Previous diagnosed condition that might mimic or complicate the course and
evaluation of the infectious disease process (severe bronchiectasis, lung abcess or empyema, aspiration pneumonia, active tuberculosis, pulmonary malignancy, cystic fibrosis, severe chronic interstitial pneumonia, severe COPD or other forms of chronic lung disease requiring home oxygen treatment)

9. Patient not expected to survive more than 30 days because of uncorrectable medical
or surgical condition other than sepsis

10.Patient with acute or chronic renal failure requiring dialysis (renal failure without need
for dialysis permitted).

11. Patient with hematological malignancies of any kind

12. Patients who have undergone transplantation of bone marrow, liver, pancreas, heart,
lung, or bowel (kidney transplant permitted)

13. Patient has known hypercoagulable condition:
APC 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
mo)

14. Patients with known congenital hypocoagulable diseases

15. Patient with known AIDS

16. Patient with known primary pulmonary hypertension