Clinical trial NCT00268996: Integrated Biomarker And Imaging Study - 2
Official title: An International, Multicenter, Randomized, Placebo-controlled, Parallel-group, 1 Year Treatment, Integrated Biomarkers and Imaging Study in Subjects With Angiographically Documented Coronary Heart Disease (CHD) to Examine the Effects of the Novel Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Inhibitor SB-480848 on Intermediate Cardiovascular Endpoints, Patient Safety and Tolerability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atherosclerosis
Keywords: Coronary artery disease
Lipoprotein-associated Phospholipase A2
palpography
hs-CRP
endothelial function
intravascular ultrasound
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-12-23
Enrollment: 336
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: IBIS-2 is a study using SB-480848 versus placebo in subjects with angiographically documented coronary heart disease. Endpoints include coronary imaging, endothelial function, biomarkers, safety and tolerability.

Detailed description: Integrated Biomarker and Imaging Study -2 (IBIS-2): An International, Multicenter, Randomized, Placebo-controlled, Parallel-group, 1 Year Treatment, Integrated Biomarkers and Imaging Study in Subjects with Angiographically Documented Coronary Heart Disease (CHD) to Examine the Effects of the Novel Lipoprotein-associated Phospholipase A2 (Lp-PLA2) inhibitor SB-480848 on Intermediate Cardiovascular Endpoints, Patient Safety and Tolerability.

Eligibility criteria: Inclusion criteria:

* Successful PCI (Percutaneous Coronary Intervention) or uncomplicated diagnostic catheterization
* Suitable non-intervened coronary artery with IVUS
* Antiplatelet therapy

Exclusion criteria:

* Clinical instability
* Previous CABG (Coronary Artery By-pass Graft) surgery
* Planned major surgery
* Recent stroke
* Abnormal QTc
* Renal or hepatic impairment
* Uncontrolled hypertension
* Use of corticosteroids
* Class III or IV heart failure
* Asthma

Primary outcomes:
measure: Mean Circulating High Sensitivity C- Reactive Protein (Hs-CRP) Levels at Week 52.
timeFrame: Week 52
measure: Change From Baseline in the Density of Rotterdam Classification (ROC) Grade III/IV Strain Spots/10 Millimeter (mm) Within the Region of Interest (ROI) on IVUS Grey Scale Based Palpography at the End of Week 52.
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: Circulating Hs-CRP at the End of Week 26.
timeFrame: Week 26
measure: Mean Lipoprotein Phospholipase A2 (Lp-PLA2) Activity at the End of Week 26 and Week 52
timeFrame: Week 26 and Week 52
measure: Change From Baseline in Plaque Volume as IVUS-Grey Scale Assessments at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Percent Obstruction Volume as IVUS-Grey Scale Assessments at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Necrotic Core Volume as Intravenous Ultrasound-Virtual Histology (IVUS-VH) Assessments at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Necrotic Core as a Percent of IVUS-VH Plaque at the End of Week 52.
timeFrame: Baseline and Week 52
measure: Mean Interlukin 6 (IL-6) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52
timeFrame: Week 26 and Week 52
measure: Mean Intercellular Adhesion Molecule-1 (ICAM-1) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52
timeFrame: Week 26 and Week 52
measure: Mean Myeloperoxidase (MPO) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52
timeFrame: Week 26 and Week 52
measure: Mean sCD40L Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52
timeFrame: Week 26 and Week 52
measure: Mean Matrix Metaloproteinases-9 (MMP-9) Levels as Circulating Biomarkers Associated With Plaque Instability at Week 26 and Week 52.
timeFrame: Week 26 and Week 52
measure: Mean Levels of Oxidised Phospholipids/ Apolipoprotein B100 (oxPL/apoB) Ratio as Target Circulating Biomarkers at the End of Week 26 and Week 52.
timeFrame: Week 26 and Week 52
measure: Mean Levels of Oxidized Non-esterified Fatty Acids (Ox-NEFA) as Target Circulating Biomarkers at the End of Week 26 and Week 52
timeFrame: Week 26 and Week 52
measure: Change From Baseline in Vessel Volume and Lumen Volume as IVUS-Grey Scale Assessments at Week 52.
timeFrame: Baseline and Week 52
measure: Change From Baseline in Mean Plaque Area, Mean Vessel Area, and Mean Lumen Area as IVUS-Grey Scale Assessments at Week 52.
timeFrame: Baseline and Week 52
measure: Change From Baseline in Fibrous Tissue Volume and Fibro-fatty Volume as IVUS-VH Assessments at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Fibrous Tissue and Fibro-fatty as a Percent of IVUS-VH Plaque as IVUS-VH Assessments at Week 52
timeFrame: Baseline and Week 52
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: GSK Investigational Site
city: Aalst
country: Belgium
facility: GSK Investigational Site
city: Antwerpen
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Praha 2
country: Czechia
facility: GSK Investigational Site
city: Aarhus N
country: Denmark
facility: GSK Investigational Site
city: Besancon
country: France
facility: GSK Investigational Site
city: Brest Cedex
country: France
facility: GSK Investigational Site
city: Heidelberg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Bad Nauheim
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bad Segeberg
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Eindhoven
country: Netherlands
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Leeuwarden
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Bergen
country: Norway
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Marid
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Luzern 16
country: Switzerland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Serruys PW, Garcia-Garcia HM, Buszman P, Erne P, Verheye S, Aschermann M, Duckers H, Bleie O, Dudek D, Botker HE, von Birgelen C, D'Amico D, Hutchinson T, Zambanini A, Mastik F, van Es GA, van der Steen AF, Vince DG, Ganz P, Hamm CW, Wijns W, Zalewski A; Integrated Biomarker and Imaging Study-2 Investigators. Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation. 2008 Sep 9;118(11):1172-82. doi: 10.1161/CIRCULATIONAHA.108.771899. Epub 2008 Sep 1.