Prevention of Cardiovascular Events (eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke) in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Full Text View

Purpose

This study is being carried out to see if a new drug called ticagrelor given twice daily in addition to the ASA therapy decreases the frequency of cardiovascular events (e.g., death from heart disease, heart attack, or stroke).

Condition	Intervention	Phase
Myocardial Infarction Cardiovascular Death Atherothrombosis Stroke	Drug: Ticagrelor 90 mg Drug: Ticagrelor 60 mg Drug: Ticagrelor Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	A Randomized, Double-Blind, Placebo Controlled, Parallel Group, Multinational Trial, to Assess the Prevention of Thrombotic Events With Ticagrelor Compared to Placebo on a Background of Acetyl Salicylic Acid (ASA) Therapy in Patients With History of Myocardial Infarction

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack

Drug Information available for: Ticagrelor

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death), Myocardial Infarction (MI) or Stroke Within 3 Years From Randomization [ Time Frame: Randomization up to 47 months ] [ Designated as safety issue: No ]
Participants with CV death, MI or Stroke. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent, non-CV death or at the last time point of complete clinical event assessment. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who experienced CV Death, MI or stroke within 3 years from randomization
Kaplan-Meier Estimate of the Percentage of Patients Who Experienced a TIMI Major Bleeding Within 3 Years From First Dose of Study Drug Units: Percentage of Patients [ Time Frame: First dosing up to 48 months ] [ Designated as safety issue: Yes ]
A Thrombolysis in Myocardial Infarction (TIMI) study group major bleeding is defined as any fatal bleeding (leading directly to death within 7 days), any intrcranial bleeding or any clinically overt signs of haemorrhage associated with a drop in Haemoglobin of >= 5g/dL. Events were adjudicated by a clinical events committee. Censoring ocurrs at 7 days following last dose of study drug. The Kaplan-Meier estimate reports the percentage of patients who experienced a TIMI Major bleeding within 3 years from first dose of study drug

Secondary Outcome Measures:

Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death) Within 3 Years From Randomization [ Time Frame: Randomization up to 47 months ] [ Designated as safety issue: No ]
Participants with CV death. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent, non-CV death or at the last time point of complete clinical event assessment. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who experienced CV Death within 3 years from randomization
Kaplan-Meier Estimate of the Percentage of Patients Who Died From Any Cause Within 3 Years From Randomization [ Time Frame: Randomization up to 47 months ] [ Designated as safety issue: No ]
Participants with death from any cause. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent or the last time point the particapant was known to be alive. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who died from any cause within 3 years from randomization


Enrollment:	21379
Study Start Date:	October 2010
Study Completion Date:	December 2014
Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Oral Treatment	Drug: Ticagrelor 90 mg Oral dose twice a day
Experimental: 2 Oral Treatment	Drug: Ticagrelor 60 mg Oral dose twice a day
Placebo Comparator: 3 Oral Treatment	Drug: Ticagrelor Placebo Oral dose twice a day

Eligibility


Ages Eligible for Study:	50 Years to 130 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Person who had a heart attack within 1 - 3 years ago and at least one additional risk factor: Age ≥ 65 years old, Diabetes requiring medication, Documented history of 2nd prior MI (>1 year ago). Angiographic evidence of multivessel CAD, and / or Chronic, non-end stage renal dysfunction.
Females of child-bearing potential must have a negative pregnancy test at enrollment
Persons who are currently taking aspirin between 75 and 150 mg once daily

Exclusion Criteria:

Persons who are being treated with agents inhibiting blood clotting if the agent cannot be stopped at study start
Persons who have planned coronary, cerebrovascular, or peripheral arterial Revascularization (invasive surgery) at study start
Persons with known bleeding disorders
Persons who need chronic oral anticoagulant therapy or chronic low-molecular-weight heparin
Persons with a history of ischemic stroke
Persons with a history of intracranial bleeding at any time, a tumor or blood vessel abnormality in the brain and/or spinal cord at any time, a history of surgery involving the brain or spinal cord within the last 5 years, or a history of bleeding from the gastrointestinal tract (eg, esophagus, stomach, colon, rectum) within the last 6 months or a major surgery within the last 30 days.
Persons considered to be at risk of bradycardic events unless already treated with a permanent pacemaker
Persons who have had open heart surgery within the past 5 years, unless the person had a heart attack after the surgery
Persons with known severe liver disease
Persons with kidney failure requiring dialysis
Persons with life expectancy < 1 year

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225562

Show 847 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators


Study Chair:	Eugene Braunwald, MD	TIMI Study Group
Principal Investigator:	Marc Sabatine, MD, MPh	TIMI Study Group

More Information

Additional Information:

D5132C00001_Protocol This link exits the ClinicalTrials.gov site

Publications:

Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015 May 7;372(19):1791-800. doi: 10.1056/NEJMoa1500857. Epub 2015 Mar 14.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bonaca MP, Bhatt DL, Steg PG, Storey RF, Cohen M, Im K, Oude Ophuis T, Budaj A, Goto S, López-Sendón J, Diaz R, Dalby A, Van de Werf F, Ardissino D, Montalescot G, Aylward P, Magnani G, Jensen EC, Held P, Braunwald E, Sabatine MS. Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54. Eur Heart J. 2016 Apr 7;37(14):1133-42. doi: 10.1093/eurheartj/ehv531. Epub 2015 Oct 21.

Bonaca MP, Bhatt DL, Braunwald E, Cohen M, Steg PG, Storey RF, Held P, Jensen EC, Sabatine MS. Design and rationale for the Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial. Am Heart J. 2014 Apr;167(4):437-444.e5. doi: 10.1016/j.ahj.2013.12.020. Epub 2014 Jan 6. Review.


Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01225562 History of Changes
Other Study ID Numbers:	D5132C00001 2009-017242-30
Study First Received:	July 9, 2010
Results First Received:	November 4, 2015
Last Updated:	December 18, 2015
Health Authority:	Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: Ministry of Social Affairs, Public Health and the Environment Brazil: National Health Surveillance Agency Bulgaria: Bulgarian Drug Agency Canada: Health Canada Chile: Instituto de Salud Pública de Chile China: Food and Drug Administration Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Czech Republic: State Institute for Drug Control France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy Italy: Ethics Committee Japan: Ministry of Health, Labor and Welfare Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Norway: Norwegian Medicines Agency Peru: Instituto Nacional de Salud Philippines: Bureau of Food and Drugs Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Romania: National Medicines Agency Russia: Pharmacological Committee, Ministry of Health Slovakia: State Institute for Drug Control South Africa: Medicines Control Council South Korea: Korea Food and Drug Administration (KFDA) Spain: Agencia Española de Medicamentos y Productos Sanitarios Sweden: Medical Products Agency Turkey: Ministry of Health Ukraine: Ministry of Health United States: Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:


Heart attack Heart Disease Acute coronary syndrome ACS Cardiovascular Disease

Additional relevant MeSH terms:


Stroke Infarction Myocardial Infarction Death Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Ischemia Pathologic Processes	Necrosis Myocardial Ischemia Heart Diseases Ticagrelor Purinergic P2Y Receptor Antagonists Purinergic P2 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016

Prevention of Cardiovascular Events (eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke) in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin (PEGASUS)