Evaluating Additional Platelet Inhibition in Patients With High Platelet Reactivity Undergoing Percutaneous Coronary Intervention

NCT01339026 | Terminated Phase 4

• 1 other identifier: 2010-020219-35
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Patients admitted to hospital with chest pain due to reduced blood flow to heart muscle (diagnosis Acute Coronary Syndrome) can be treated with medication and an angioplasty ± stent procedure, which restores blood flow to the heart. Antiplatelet drugs (Aspirin and Clopidogrel) are blood thinning treatments and research has reported they reduce heart attacks, death and stroke. The investigators know some patients do not respond fully to Clopidogrel but currently patients are not tested for this. The investigators wish to perform a trial to identify those patients who do not respond fully to Clopidogrel and randomise them to either Prasugrel (newer drug) or a higher dose of Clopidogrel. Patients admitted to the hospitals (2 in the UK and 1 in Germany) will be asked for their consent to participate. A blood sample is tested for platelet activity.

1. 1.Low platelet activity result means patient has responded well to Clopidogrel and will continue on the routine dose. They will be entered into an observational registry. Data will be collected of routine blood tests and investigations, medication and procedures. Their GP will be contacted at about 30 days to see if they are alive.
2. 2.High platelet activity results means patient has not responded fully to Clopidogrel. These patients will be randomly allocated to a higher dose of Clopidogrel or new drug Prasugrel. Data will be collected of routine blood tests and investigations, medication and procedures. A hospital visit at 30±5 days is required to assess how patients are doing, medications and occurrence of any events.

Conditions

Cardiovascular Disease; Acute Coronary Syndrome

Keywords

Acute coronary syndrome; Platelet reactivity; Clopidogrel; Percutaneous coronary intervention

Outcome Measures

Primary Outcomes (1)

• Platelet Reactivity

  The primary endpoint will compare the proportion of patients with improved platelet response (i.e. decreased platelet reactivity under the cut-off value of 400 Au.min) in the prasugrel re-loading arm compared to the clopidogrel re-loading arm at 4 hours after randomization in patients with initial high platelet reactivity

  4 hours post loading dose

Secondary Outcomes (4)

• Platelet reactivity in response to randomised study drug

  7 days/hospital discharge and 30 days

• Extent of myocardial damage

  24 hours

• MACE

  30 days

• Bleed

  30 days

Study Arms (2)

Prasugrel

ACTIVE COMPARATOR

Day 1 loading 60mg Day 2 to 7 10mg o.d. Day 8 to 30 days 10mg od

Drug: Prasugrel

Clopidogrel

ACTIVE COMPARATOR

Day 1 Loading 600mg Day 2 to 7 day: 150mg o.d. Day 8 to 30 days: 75mg o.d.

Drug: Plavix

Interventions

Prasugrel DRUG

Day 1 loading 60mg Day 2 to 7 10mg o.d. Day 8 to 30 days 10mg od

Also known as: Efient

Prasugrel

Plavix DRUG

Clopidogrel (Plavix) Day 1 Loading 600mg Day 2 to 7 day: 150mg o.d. Day 8 to 30 days: 75mg o.d.

Also known as: Clopidogrel

Clopidogrel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ACS patients with intent for PCI \<72 hours from admission.
• Prior clopidogrel loading within 24h before planned PCI or chronic (\>24 hours) treatment with clopidogrel
• High platelet reactivity (HPR) PA \> 400 AU min by multiplate analyser ("poor responders")
• Initial platelet function sample at least 2 hours after pre PCI loading dose
• Consent

You may not qualify if:

• Patients \<18 years and \>75 years
• Body weight \<60kg
• Pretreatment with prasugrel within 7 days of randomisation
• History of stroke or transient ischaemic attack
• Patients with increased bleeding risk e.g.
• recent major trauma or surgery
• gastrointestinal bleeding or active peptic ulceration
• Platelet count \<100,000 / mm3 at the time of screening
• Internationally Normalized Ratio (INR)\> 1.5 at the time of screening
• Hb\<10g/dL
• Intracranial neoplasm, arteriovenous malformation or aneurysm.
• Severe hepatic impairment (Child Pugh class C)
• Intention to use the following medications
• oral anticoagulation
• other antiplatelet therapy (including GPIIb/IIIa inhibitors) besides aspirin

Sponsors & Collaborators

• Royal Brompton & Harefield NHS Foundation Trust: lead
• University Hospital Tuebingen: collaborator

Study Sites (1)

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Related Publications (1)

• Geisler T, Booth J, Tavlaki E, Karathanos A, Muller K, Droppa M, Gawaz M, Yanez-Lopez M, Davidson SJ, Stables RH, Banya W, Zaman A, Flather M, Dalby M. High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel. PLoS One. 2015 Aug 28;10(8):e0135037. doi: 10.1371/journal.pone.0135037. eCollection 2015.

  PMID: 26317618 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Acute Coronary Syndrome

Interventions

Prasugrel Hydrochloride; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Miles Dalby, MD

  Royal Brompton & Harefield NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Tobias Geisler, MD

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

• Azfar Zaman, MD

  Freeman Hospital and University of Newcastle

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2011
• First Posted: April 20, 2011
• Study Start: February 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 18, 2014

Record last verified: 2014-09

Locations

DE (1)