NCT00799903: STABILITY

The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial

Completed Phase 3 Results posted Last updated 10 August 2017

What this trial tests

Phase 3 trial testing Darapladib in Atherosclerosis in 15,828 participants. Completed in 17 October 2013.

Timeline

1 December 2008

Primary endpoint
1 October 2013

17 October 2013

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	15,828
Start date	1 December 2008
Primary completion	1 October 2013
Estimated completion	17 October 2013
Sites	650 locations across Hong Kong, Italy, Japan, Taiwan, Poland, South Korea, Philippines, Denmark

Drugs / interventions tested

• Darapladib — full drug profile →
• Placebo

Conditions studied

• Atherosclerosis — all drugs for Atherosclerosis →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Atherosclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With First Occurrence of Any Component of the Composite of Major Adverse Cardiovascular Events (Cardiovascular [CV] Death, Non-fatal Myocardial Infarction [MI] or Non-fatal Stroke) During the Time Period for Follow-up of CV Events Primary · From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years)

CV death=death due to a CV cause, which included but was not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss o

Group	Value	95% CI
Placebo	819
Darapladib	769

Number of Participants With First Occurrence of Any Event in the Composite of Major Coronary Events (Coronary Heart Disease [CHD] Death, Non-fatal MI, or Urgent Coronary Revascularization [CR] for MI) During the Time Period for Follow-up (FU) of CV Events Secondary · From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years)

CHD death=occurrence of a fatal MI, death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g.,silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic

Group	Value	95% CI
Placebo	814
Darapladib	737

Number of Participants With First Occurrence of Any Event in the Composite of Total Coronary Events (CHD Death, Non-fatal MI, Hospitalization for Unstable Angina, or Any Coronary Revascularization Procedure) During Time Period for FU of CV Events Secondary · From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years)

CHD death, acute MI, and prior MI are defined in the previous secondary endpoint (major coronary events). Hospitalization for unstable angina=one of the following, but not fulfilling the criteria for MI: ischemic discomfort at rest associated with electrocardiogram (ECG) changes leading to hospitalization; ischemic discomfort at rest regardless of ECG changes leading to hospitalization and revascularization during the same admission; ischemic discomfort at rest in hospital associated with ECG changes; ischemic discomfort at rest in hospital without ECG changes resulting in revascularization du

Group	Value	95% CI
Placebo	1269
Darapladib	1159

Number of Participants With CV Death During the Time Period for Follow-up of CV Events Secondary · From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years)

CV death is defined as a death due to a CV cause, which included but was not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths.

Group	Value	95% CI
Placebo	373
Darapladib	359

Number of Participants With First Occurrence of MI (Fatal/Non-fatal) During the Time Period for Follow-up of CV Events Secondary · From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years)

Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI.

Group	Value	95% CI
Placebo	405
Darapladib	361

Number of Participants With First Occurrence of Stroke (Fatal/Non-fatal) During the Time Period for Follow-up of CV Events Secondary · From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years)

Stroke is defined as the presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting \>24 hours or results in death (in \<24 hours).

Group	Value	95% CI
Placebo	152
Darapladib	154

Number of Participants With First Occurrence of Any Component of the Composite of All-cause Mortality, Non-fatal MI, or Non-fatal Stroke During the Time Period for Follow-up of CV Events Secondary · From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years)

Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms l

Group	Value	95% CI
Placebo	962
Darapladib	926

Number of Participants With All-cause Mortality During the Time Period for Vital Status Secondary · From randomization until death or study completion (up to 4.49 years/average of 3.65 years)

The number of participants with all-cause mortality was assessed.

Group	Value	95% CI
Placebo	577
Darapladib	582

Adverse events — posted to ClinicalTrials.gov

Time frame: Start=Randomization; Stop=Longer of 35 days after last dose of IP or follow-up (FU) visit. "SAEs assessed as related to IP, study participation, or a GSK concomitant medication" and cancer/GI polyps/neoplasms were recorded up to/including any FU contact.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 3448/7890 (44%)

Deaths: 577/7904

Darapladib

Serious: 3369/7912 (43%)

Deaths: 582/7924

Serious adverse events (1627 terms)

Reaction	System	Placebo	Darapladib
Angina unstable	Cardiac disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Angina pectoris	Cardiac disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Cardiac failure	Cardiac disorders	—	—
Coronary artery disease	Cardiac disorders	—	—
Pneumonia	Infections and infestations	—	—
Cardiac failure congestive	Cardiac disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Ischaemic stroke	Nervous system disorders	—	—
Transient ischaemic attack	Nervous system disorders	—	—
Renal failure acute	Renal and urinary disorders	—	—
Syncope	Nervous system disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Death	General disorders	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Coronary artery stenosis	Cardiac disorders	—	—
Sudden death	General disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
Peripheral arterial occlusive disease	Vascular disorders	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Carotid artery stenosis	Nervous system disorders	—	—
Inguinal hernia	Gastrointestinal disorders	—	—

Other adverse events (43 terms — click to expand)

Reaction	System	Placebo	Darapladib
Diarrhoea	Gastrointestinal disorders	—	—
Abnormal faeces	Gastrointestinal disorders	—	—
Hypertension	Vascular disorders	—	—
Type 2 diabetes mellitus	Metabolism and nutrition disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Angina pectoris	Cardiac disorders	—	—
Dizziness	Nervous system disorders	—	—
Urine odour abnormal	Renal and urinary disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Oedema peripheral	General disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Bronchitis	Infections and infestations	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Skin odour abnormal	Skin and subcutaneous tissue disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Fatigue	General disorders	—	—
Headache	Nervous system disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Large intestine polyp	Gastrointestinal disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Influenza	Infections and infestations	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Cataract	Eye disorders	—	—
Blood pressure increased	Investigations	—	—
Gastritis	Gastrointestinal disorders	—	—
Flatulence	Gastrointestinal disorders	—	—
Sinusitis	Infections and infestations	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Hypotension	Vascular disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Blood glucose increased	Investigations	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: Angina unstable, Acute myocardial infarction, Angina pectoris, Non-cardiac chest pain, Cardiac failure, Coronary artery disease, Pneumonia, Cardiac failure congestive.

Data from ClinicalTrials.gov NCT00799903 adverse events section.

Sponsor's own description

This study will test whether darapladib can safely lower the chances of having a cardiovascular event (such as a heart attack or stroke) in people with coronary heart disease.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Eicosanoid storm in infection and inflammation.
   Dennis EA, Norris PC. · · 2015 · cited 1139× · PMID 26139350 · DOI 10.1038/nri3859
2. Phospholipase A2 enzymes: physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention.
   Dennis EA, Cao J, Hsu YH, Magrioti V, et al · · 2011 · cited 883× · PMID 21910409 · DOI 10.1021/cr200085w
3. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention.
   Kong P, Cui ZY, Huang XF, Zhang DD, et al · · 2022 · cited 749× · PMID 35459215 · DOI 10.1038/s41392-022-00955-7
4. Darapladib for preventing ischemic events in stable coronary heart disease.
   STABILITY Investigators, White HD, Held C, Stewart R, et al · · 2014 · cited 417× · PMID 24678955 · DOI 10.1056/nejmoa1315878
5. The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation.
   Hijazi Z, Lindbäck J, Alexander JH, Hanna M, et al · · 2016 · cited 307× · PMID 26920728 · DOI 10.1093/eurheartj/ehw054
6. Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial.
   Held C, White HD, Stewart RAH, Budaj A, et al · · 2017 · cited 187× · PMID 29066452 · DOI 10.1161/jaha.116.005077
7. Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease.
   Lindholm D, Lindbäck J, Armstrong PW, Budaj A, et al · · 2017 · cited 103× · PMID 28797349 · DOI 10.1016/j.jacc.2017.06.030
8. Plasma proteins associated with cardiovascular death in patients with chronic coronary heart disease: A retrospective study.
   Wallentin L, Eriksson N, Olszowka M, Grammer TB, et al · · 2021 · cited 97× · PMID 33439866 · DOI 10.1371/journal.pmed.1003513