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

Sponsor

Thrombologic ApS (Industry)

Overall Status

Terminated

CT.gov ID

NCT01532544

Collaborator

Anders Perner (Other), Rigshospitalet, Denmark (Other)

Enrollment

Locations

Arms

Duration (Months)

1.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia	Drug: Ilomedin and Integrilin Drug: low molecular weight heparin.	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Mar 1, 2014

Actual Study Completion Date :

Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Integrilin and Ilomedin given as continous infusion	Drug: Ilomedin and Integrilin Continuous infusion Other Names: Integrilin and Ilomedin
Placebo Comparator: Standard treatment daily doses of low molecular weight heparin Standard treatment daily doses of low molecular weight heparin.	Drug: low molecular weight heparin.

Arm

Intervention/Treatment

Experimental: Integrilin and Ilomedin given as continous infusion

Drug: Ilomedin and Integrilin

Continuous infusion

Other Names:

Integrilin and Ilomedin

Placebo Comparator: Standard treatment daily doses of low molecular weight heparin

Standard treatment daily doses of low molecular weight heparin.

Drug: low molecular weight heparin.

Outcome Measures

Primary Outcome Measures

Change in platelet count from baseline to 72 hours post treatment [11 bloodsamples over 7 days]
Will be from pre-study drug administration until 7 days

Secondary Outcome Measures

Severe bleeding (intracranial or clinical bleeding with the use of 3 RBC units or more) (KyperSept trial) [7 days]
If longer in the ICU ward followed until discharged.
Days of vasopressor, ventilator and renal replacement therapy and use of blood product (in ICU) after randomization [7 days]
Followed longer if not discharged from the ICU at day 7

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

At least 18 years of age AND
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.

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

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
Can be randomized into trial and dosed < 48 h after severe sepsis diagnosis AND
Consent is obtainable -

Exclusion Criteria:

Patient is pregnant or breast-feeding
Patient weigh 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
Investigators clinical decision deeming study participation not favourable for the patient
Patients in whom the clinician finds antithrombotic therapy contraindicated - prophylaxis included
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.
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.

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.)
Patient not expected to survive more than 30 days because of uncorrectable medical or surgical condition other than sepsis
Patient with acute or chronic renal failure requiring dialysis (renal failure without need for dialysis permitted).
Patient with hematological malignancies of any kind
Patients who have undergone transplantation of bone marrow, liver, pancreas, heart, lung, or bowel (kidney transplant permitted)
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)

Patients with known congenital hypocoagulable diseases
Patient with known AIDS
Patient with known primary pulmonary hypertension

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University hospital Copenhagen	Copenhagen	Denmark	2100
2	Vejle hospital	Vejle	Denmark
3	Kuopio University Hospital	Kuopio	Finland
4	Tampere University Hospital	Tampere	Finland	33521