Early Percutaneous Coronary Intervention (PCI) After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction (STEMI) Patients

November 13, 2009 updated by: Royal Brompton & Harefield NHS Foundation Trust

Early Invasive Strategy After Fibrinolysis vs Standard Management in STEMI Patients: Results From an Individual Patient Data Meta-analysis (OTTER Meta-analysis) OTTER: Optimal Timing for Post-Thrombolysis Elective Revascularization

Several recent trials (1,2) suggest that all STEMI patients receiving fibrinolysis in non-PCI centres should be routinely transferred for elective early PCI within 24 hours from hospitalization, with no additive risk of major bleeding complications or other severe adverse events compared standard therapy. These results in favour of a routine invasive strategy in STEMI patients suggest a potential change to the current approach of awaiting the response to treatment in patients receiving fibrinolysis, and draw the attention to the potential need for an appropriate network organization with adequate first hospitalization treatment (spoke) and prompt transfer to centres with 24/7 PCI capabilities (hub). The recent ESC (3) and ACC (4) guidelines on STEMI are consistent with the early ESC PCI Guidelines, recommending that angioplasty after fibrinolysis should be performed within a time-window ranging between 3 and 24 hours after successful lytic administration (level evidence IIA). The reason for the weighting of the recommendation is due to the heterogeneity of trial results with different planned-revascularization strategies, variable primary end-points definitions, and small individual trial sample sizes. Therefore, a consistent analysis of single patient dataset from all published randomized trials would be of value to better define the magnitude and duration of clinical benefit of the routine invasive strategy after lytic treatment as well as the potential optimal timing of such a strategy.

The main aim of the OTTER meta-analysis is to define the benefits of immediate PCI after fibrinolysis for STEMI patients. Moreover, the OTTER meta-analysis will investigate the optimal timing of post-fibrinolysis elective revascularization.

Study Overview

Status

Unknown

Conditions

Detailed Description

All published randomized controlled trials that compared a routine invasive strategy with early PCI and a standard therapy in STEMI patients after fibrinolysis will be included in this analysis.

We will exclude all non-randomized trials, randomized studies if the individual patient data will not be available for analysis, randomized studies in which angioplasty was mainly performed without stenting (<80% stenting population) and in which the type of lytic therapy was different from modern fibrin-specific agents. Two investigators independently will evaluate studies for possible inclusion. The quality of searched trials will be evaluated based on the 5-point scale outlined by Jadad et al (5), with criteria for randomization with proper concealment of the allocation sequence, blinding of the patient and investigators to treatment allocation with description of the blinding method, and completeness of follow-up.

Recruitment:

An electronic database will be compiled consisting of data from each single patient of all enrolled trials, according to the guidelines for the performance of individual patient meta-analysis.(6-7-8). The database will include demographic data and baseline characteristics. Attention will be paid to clinical complications during transfer for early PCI and to the precise calculation of the following times-window: from symptoms onset to lytic therapy, from lytic therapy to early or rescue PCI, from randomization to all adverse events as defined below. Data will be checked for completeness and for consistency with published reports. Two investigators independently will extract all data, with disagreements resolved in consultation with a third investigator.

End-points

The following end-points will be investigated:

Primary End Point: Combined death/reinfarction at 30 days.

Secondary end-points:

  • Death, reinfarction, recurrent ischemia and urgent revascularization at 30 days.
  • Combined death/reinfarction/recurrent ischemia/urgent revascularization and new presentation CHF and shock at 30 days.
  • Major bleeding and hemorrhagic stroke at 30 days.
  • Combined death/reinfarction and combined revascularization/recurrent ischemia at 6-12 months.

Secondary analysis will also investigate the influence of the timing of post-thrombolysis early revascularization on the above considered events.

Investigators: The study is coordinated by Prof. C. Di Mario. An executive committee composed of the Principle Investigators of the enrolled trials will overview the quality of data collected (OTTER Investigators). No publication will be sent without written consent of all the PIs of the individual trials. Statistical analysis will be performed at the Royal Brompton Hospital (London) and the Canadian Heart Research Centre (Toronto, Ontario, Canada).

References:

  1. Cantor WJ, Fitchett D, Borgundvaag B, Ducas J, et al. TRANSFER-AMI Trial Investigators. Routine early angioplasty after fibrinolysis for acute myocardial infarction. N Engl J Med. 2009 Jun 25;360(26):2705-18.
  2. Di Mario C, Dudek D, Piscione F, et al. Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomized, multicentre trial. Lancet 2008; 371:559-568.
  3. Van de Werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J 2008; 29:2909-2945.
  4. Antman EM, Hand M, Armstrong PW, et al. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008; 51:210-247.
  5. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996 Feb;17(1):1-12.
  6. Simmonds MC, Higgins JP, Stewart LA, et al. Meta-analysis of individual patient data from randomized trials: a review of methods used in practice. Clin Trials. 2005;2(3):209-17.
  7. Clarke MJ, Stewart LA. Meta-analyses using individual patient data. J Eval Clin Pract. 1997 Aug;3 (3):207-12. Review. PubMed PMID: 9406108
  8. Stewart LA, Clarke MJ. Practical methodology of meta-analyses (overviews) using updated individual patient data. Cochrane Working Group. Stat Med. 1995 Oct 15;14(19):2057-79.

Study Type

Observational

Enrollment (Anticipated)

3000

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

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

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

STEMI patients.

Description

Inclusion Criteria:

  • STEMI patients enrolled within 12 hours from onset of symptoms
  • Controlled randomized trials comparing a routine invasive strategy with standard therapy in STEMI patients
  • Modern fibrin-specific therapy in both groups
  • Stenting PCI > 80% of invasive procedures
  • English language

Exclusion Criteria:

  • Cardiogenic shock at presentation
  • Need for concomitant
  • Major surgery
  • Severe chronic renal or hepatic impairment
  • Myocardial infarction within the previous 2 weeks
  • Contraindications to thrombolytic therapy, abciximab, aspirin, or clopidogrel
  • Non randomized trials
  • Single patient data not available
  • Non fibrin-specific lytic therapy
  • Stenting PCI < 80% of invasive procedures
  • Not English language

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?

Cohorts and Interventions

Group / Cohort
Early PCI
Routine invasive strategy with early PCI performed in STEMI patients within 24 hours from successful fibrinolysis
Standard Therapy
Standard therapy in STEMI patients with fibrinolysis and/or conventional ischaemic-guided therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Combined death/reinfarction
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Death, reinfarction, recurrent ischemia and urgent revascularization
Time Frame: 30 days
30 days
Combined death/reinfarction/recurrent ischemia/urgent revascularization and new presentation CHF and shock
Time Frame: 30 days.
30 days.
Major bleeding and hemorrhagic stroke
Time Frame: 30 days
30 days
Combined death/reinfarction and combined revascularization/recurrent ischemia
Time Frame: 6-12 months
6-12 months
Influence of Optimal Timing of Post-Thrombolysis early revascularization on primary and secondary clinical end-points
Time Frame: 0-24 hours from thrombolysis
0-24 hours from thrombolysis

Collaborators and Investigators

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

Sponsor

Royal Brompton & Harefield NHS Foundation Trust

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

November 1, 2009

Primary Completion (Anticipated)

December 1, 2009

Study Completion (Anticipated)

December 1, 2009

Study Registration Dates

First Submitted

November 13, 2009

First Submitted That Met QC Criteria

November 13, 2009

First Posted (Estimate)

November 16, 2009

Study Record Updates

Last Update Posted (Estimate)

November 16, 2009

Last Update Submitted That Met QC Criteria

November 13, 2009

Last Verified

November 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OTTER220179

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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