Integrilin and Ilomedin in Combination in Comparison to Standard Treatment in Severe Pneumonia Patients With Severe Sepsis

Pneumonia Clinical Trial

Official title:

Double-blinded, Randomized Trial in Severe Pneumonia Patients With Severe Sepsis Investigating the Safety and Efficacy of Co-administration of Iloprost and Ascending Doses of Eptifibatide Compared to Low-molecular-weight Heparin

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT01532544
• Other study ID #: THR-PS-03
• Secondary ID: 2011-002254-31
• Status: Suspended
• Phase: Phase 2
• First received: January 30, 2012
• Last updated: September 4, 2013
• Start date: June 2012
• Est. completion date: March 2014

Study information

• Verified date: September 2013
• Source: Thrombologic ApS
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyFinland: Data Protection BoardFinland: Ethics CommitteeFinland: Finnish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

This is an investigator sponsored double-blinded, multinational, multi center, randomized (2:1 active:placebo), placebo-controlled, phase IIa trial in severe pneumonia patients with severe sepsis or septic shock, investigating the safety and efficacy of co-administration of Iloprost and escalating doses of Eptifibatide for continuous intravenous infusion in totally 36 patients.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 36
• Est. completion date: March 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 </= 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 PaC02 < 4.2 kPa

• WBC >/= 12,000/mm³ OR </= 4,000/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 -

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 12 h, expected surgery within 72 h, epidural or spinal puncture in the previous 12 h, platelet count less than 30,000/mm3 in the previous 24 h, INR above 2.0 in the previous 24 h, need of blood products for bleeding in the previous 24 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,

• unfractionated heparin within 8 hours before the infusion (prophylactic heparin up to 15,000 U/day permitted).

• Low-molecular-weight heparin within 12 hours (prophylactic doses permitted).

• exceeded the upper limit of normal.

• 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).

• Glycoprotein IIb-IIIa antagonists within 7 days before the study.

• Antithrombin III with dose greater than 10,000 U within 12 hours before the study.

• 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, COPD or other forms of chronic lung disease requiring home oxygen treatment or resulting in chronic CO2 retention, , etc.)

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 months)

14. Patients with known congenital hypocoagulable diseases

15. Patient with known AIDS

16. Patient with known primary pulmonary hypertension

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pneumonia

Intervention

Drug:
• Ilomedin and Integrilin
Continuous infusion
• low molecular weight heparin.

Locations

Country	Name	City	State
Denmark	University hospital Copenhagen	Copenhagen
Denmark	Vejle hospital	Vejle
Finland	Kuopio University Hospital	Kuopio
Finland	Tampere University Hospital	Tampere

Sponsors (3)

Lead Sponsor	Collaborator
Thrombologic ApS	Anders Perner, Rigshospitalet, Denmark

Countries where clinical trial is conducted

Denmark,  Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in platelet count from baseline to 72 hours post treatment	Will be from pre-study drug administration until 7 days	11 bloodsamples over 7 days	Yes
Secondary	Severe bleeding (intracranial or clinical bleeding with the use of 3 RBC units or more) (KyperSept trial)	If longer in the ICU ward followed until discharged.	7 days	Yes
Secondary	Days of vasopressor, ventilator and renal replacement therapy and use of blood product (in ICU) after randomization	Followed longer if not discharged from the ICU at day 7	7 days	Yes