Reduced Dose of Unfractionated Heparin in Patients Undergoing PCI (ISAR-REACT-3A)

January 3, 2012 updated by: Deutsches Herzzentrum Muenchen

Non-randomized, Open-label, Historical Control, Single Group Assignment Trial of a Reduced Dose of Unfractionated Heparin in Patients Undergoing Percutaneous Coronary Interventions

The aim of this trial is to evaluate whether a reduction in the heparin dose from 140 to 100 U/kg is associated with a better net clinical outcome in patients undergoing PCI after pretreatment with 600mg clopidogrel

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Percutaneous coronary interventions, mostly with implantation of bare-metal or drug-eluting stents, are commonly used to treat patients with coronary artery disease. Various periprocedural adjunct antithrombotic therapies have been investigated and are being used. Unfractionated heparin (UFH) has been the standard adjunctive antithrombin therapy during PCI for more than 25 years. Combined antiplatelet treatment consisting of aspirin and a thienopyridine has significantly reduced early ischaemic events following coronary stenting (1). Thienopyridines act by irreversibly inhibiting the platelet adenosine diphosphate (ADP) P2Y12 receptor. Compared to ticlopidine, clopidogrel has the advantage of a more favourable side effect profile (2) and more rapid onset of action.(3,4) Pretreatment with a loading dose of 300mg clopidogrel improved outcomes (5-7) and is recommended by current guidelines for patients undergoing PCI. (8) More recently, trials have shown that the larger loading dose of 600mg achieves more rapid and more potent inhibition of platelet aggregation than 300 mg do.(9-11) The results of several randomized controlled trials suggest that pretreatment with 600mg clopidogrel might obviate the need for IIb/IIIa inhibitors in a broad spectrum of patients undergoing PCI (12-14) although no formal direct comparison of different clopidogrel doses has been assessed by trials sufficiently powered for clinical endpoints. The Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment (ISAR-REACT) trial showed that after pretreatment with 600mg clopidogrel for at least 2 hours before the intervention, additional use of abciximab was not associated with any clinically measurable benefit among low-to-intermediate risk patients who underwent PCI.(12) Even in higher risk settings such as small vessel size (14) and the presence of diabetes (13)additional use of abciximab was not associated with a measurable clinical benefit in patients pretreated with 600mg clopidogrel. An important exception is the group of patients with non-ST-segment elevation ACS. In the ISAR-REACT-2 trial that enrolled this category of patients those with an elevated troponin level did benefit from abciximab even after pretreatment with 600mg clopidogrel.(15) The recently completed ISAR-REACT-3 trial compared unfractionated heparin with the direct thrombin inhibitor bivalirudin in biomarker negative patients with stable and unstable angina undergoing contemporary PCI. Bivalirudin did not provide "net clinical benefit" - did not reduce the quadruple endpoint - at 30 days compared to unfractionated heparin. However, there was a significant reduction in bleeding with bivalirudin (16) The heparin dose regimen used in ISAR-REACT-3 diverges from current US practice insofar as the majority of patients received a bolus dose of 140 U/kg with no follow up ACT measurement and no additional heparin doses. Although heparin has been the standard antithrombin therapy in interventional cardiology for decades, its optimal dose is still not known. During the last years there has been a trend towards using lower heparin doses. In most interventional trials in the United States it is now current practice to use a bolus of not more than 100 U/kg. (8) Many interventionalists believe that a dose lower than 140 U/kg is associated with a better clinical outcome. However, no studies have been performed to identify the most appropriate dose of heparin. Since pretreatment with clopidogrel has proven to reduce ischemic events, a heparin dose of 140U/kg might conceivably be too high. A lower dose might prove to be as effective in preventing ischemic endpoints while reducing the risk of bleeding if patients were pretreated with 600mg clopidogrel prior to the intervention. Therefore the aim of this trial is to evaluate whether a reduction in the heparin dose from 140 to 100 U/kg is associated with a better net clinical outcome in patients undergoing PCI after pretreatment with 600mg clopidogrel. The hypothesis to be tested is whether a reduced dose of 100U/kg heparin is superior to the higher dose of 140U/kg used in the ISAR-REACT-3 trial (historical control) regarding the combined incidence of death, myocardial infarction, urgent target vessel revascularization within 30 days and in hospital major bleeding. The ISAR-REACT-3a trial will enroll a patient population with a similar risk profile to that of patients included in ISAR-REACT-3. Biomarker negative patients with stable or unstable angina undergoing PCI will receive a reduced dose heparin bolus of 100U/kg. Results will be compared with the ISAR-REACT-3 trial (historical control). Primary comparison will be with the heparin arm of ISAR-REACT-3 regarding the primary endpoint ("Net clinical benefit", the combined incidence of death, myocardial infarction, urgent target vessel revascularization within 30 days and in hospital major bleeding). A secondary aspect will be the comparison with the historical bivalirudin group of the ISAR-REACT-3 trial.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2505

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bad Krozingen, Germany, 79189
        • Herz-Zentrum
      • München, Germany, 81675
        • Klinikum rechts der Isar der Technischen Universität München
      • München, Germany, 81541
        • Deutsches Herzzentrum München

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients older than 18 years undergoing a PCI procedure
  2. Pretreatment with 600mg clopidogrel at least 2 hours before the intervention
  3. Informed, written consent by the patient or her/his legally-authorized representative for participation in the study.

Exclusion Criteria:

  1. Recent ST-elevation myocardial infarction within the last 48 hours
  2. Acute coronary syndromes with positive biomarkers (Troponin T > 0.03 μg/L or CK-MB > ULN)
  3. Cardiogenic shock
  4. Malignancies or other comorbid conditions (for example severe liver, renal and pancreatic disease) with life expectancy less than one year or that may result in protocol non-compliance
  5. Active bleeding; bleeding diathesis
  6. History of gastrointestinal or genitourinary bleeding within the last 6 weeks
  7. Presence of diseases which have a high probability of vascular lesions and subsequent bleeding such as active gastric ulcer or active ulcerous colitis
  8. Recent trauma or major surgery in the last month
  9. Ophthalmic surgery or brain surgery in the last month
  10. Retinopathies or vitreous body bleeding in the last month
  11. History of intracranial bleeding or structural abnormalities (for example aneurysm of cerebral arteries)
  12. Suspected aortic dissection; pericarditis and subacute bacterial endocarditis
  13. Patient's refusal to blood transfusion.
  14. Oral anticoagulation therapy with coumarin derivative within the last 7 days
  15. Treatment with UFH within 6 hours unless an ACT is less than 150 sec or low-molecular weight heparin within 8 hours before enrollment
  16. Treatment with bivalirudin within 24 hours before enrollment
  17. Severe uncontrolled hypertension >180/110 mmHg unresponsive to therapy
  18. Planned staged PCI procedure within 30 days from index procedure or prior PCI within the last 30 days.
  19. Relevant hematologic deviations: hemoglobin < 100 g/L, platelet count < 100 x 109 /L.
  20. Glomerular filtration rate (GFR) < 30 ml/min or serum creatinine > 30 mg/L or dependence on renal dialysis.
  21. Known allergy to the study medications: aspirin, clopidogrel, UFH, true anaphylaxis after prior exposure to contrast media.
  22. Known heparin-induced thrombocytopenia (Typ II)
  23. Previous enrollment in this trial.
  24. Pregnancy (present, suspected or planned) or positive pregnancy test.
  25. Spinal, peridural and epidural anesthesia
  26. Patient's inability to fully cooperate with the study protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Reduced dose of unfractionated heparin
Drug: unfractionated heparin
bolus of 100 U/kg of unfractionated heparin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The primary outcome measure will be a composite of death, MI, urgent TVR after 30 days or in hospital bleeding (quadruple endpoint, "net clinical benefit").
Time Frame: 30 days
30 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Composite of death, MI or urgent TVR (Triple endpoint to assess ischemic complications)
Time Frame: 30 days
30 days
Composite of death, MI or TVR
Time Frame: 1 year after the index procedure
1 year after the index procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Deutsches Herzzentrum Muenchen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Julinda Mehilli, MD, Deutsches Herzzentrum München

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 12, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 14, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 5, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GE IDE No. A01408

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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