Myocardial InfarctionNCT01014182
Early Percutaneous Coronary Intervention (PCI) After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction (STEMI) Patients
An observational study of Myocardial Infarction, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Myocardial Infarction
- How many people
- 3,000 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2009to Dec 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: STEMI patients.
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- Non randomized trials
- Single patient data not available
- Non fibrin-specific lytic therapy
- Stenting PCI < 80% of invasive procedures
- Not English language
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Brompton Hospital
London, SW6 3NP
Carlo Di Mario, 0044 20 7351 ext. 8616, c.dimario@rbht.nhs.uk
About this study
Official title: 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.
Read the 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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Clarke MJ, Stewart LA. Meta-analyses using individual patient data. J Eval Clin Pract. 1997 Aug;3 (3):207-12. Review. PubMed PMID: 9406108
- 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.
- Conditions
- Myocardial Infarction
- Keywords
- Early PCI, Myocardial Infarction, Thrombolysis, Optimal revascularization therapy in STEMI patients
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Combined death/reinfarction
Measured: 30 days
Secondary outcomes (5)
Death, reinfarction, recurrent ischemia and urgent revascularization
Measured: 30 days
Combined death/reinfarction/recurrent ischemia/urgent revascularization and new presentation CHF and shock
Measured: 30 days.
Major bleeding and hemorrhagic stroke
Measured: 30 days
Combined death/reinfarction and combined revascularization/recurrent ischemia
Measured: 6-12 months
Influence of Optimal Timing of Post-Thrombolysis early revascularization on primary and secondary clinical end-points
Measured: 0-24 hours from thrombolysis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2009 (estimated)
- Study startNov 2009
- Primary completionDec 2009 (estimated)
- Study completionDec 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 3,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01014182
- Sponsor's protocol ID
- OTTER220179
- Status last verified
- Nov 2009
- First submitted
- 13 Nov 2009
- Last updated
- 16 Nov 2009
- Results posted
- No
Publications
Abdel-Qadir H, Yan AT, Tan M, Borgia F, Piscione F, Di Mario C, Halvorsen S, Cantor WJ, Westerhout CM, Scheller B, Le May MR, Fernandez-Aviles F, Sanchez PL, Lee DS, Goodman SG. Consistency of benefit from an early invasive strategy after fibrinolysis: a patient-level meta-analysis. Heart. 2015 Oct;101(19):1554-61. doi: 10.1136/heartjnl-2015-307815. Epub 2015 Jul 14.
PubMed 26175478Madan M, Halvorsen S, Di Mario C, Tan M, Westerhout CM, Cantor WJ, Le May MR, Borgia F, Piscione F, Scheller B, Armstrong PW, Fernandez-Aviles F, Sanchez PL, Graham JJ, Yan AT, Goodman SG. Relationship between time to invasive assessment and clinical outcomes of patients undergoing an early invasive strategy after fibrinolysis for ST-segment elevation myocardial infarction: a patient-level analysis of the randomized early routine invasive clinical trials. JACC Cardiovasc Interv. 2015 Jan;8(1 Pt B):166-174. doi: 10.1016/j.jcin.2014.09.005. Epub 2014 Oct 31.
PubMed 25616922
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01014182
- Acronym / sponsor ID
- OTTER220179
- Conditions
- Myocardial Infarction
- Keywords
- Early PCI, Myocardial Infarction, Thrombolysis, Optimal revascularization therapy in STEMI patients
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation TrustUniversity, hospital or other
- Study start
- Nov 2009
- Primary completion
- Dec 2009 (estimated)
- Study completion
- Dec 2009 (estimated)
- First posted
- 16 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Clarke MJ, Stewart LA. Meta-analyses using individual patient data. J Eval Clin Pract. 1997 Aug;3 (3):207-12. Review. PubMed PMID: 9406108
- 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 design
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- STEMI patients.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- Cardiogenic shock at presentation
- Need for concomitant
- Major surgery
- Severe chronic renal or hepatic impairment
- Myocardial infarction within the previous 2 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Combined death/reinfarction
Time frame: 30 days
5 secondary outcomes
Death, reinfarction, recurrent ischemia and urgent revascularization
Time frame: 30 days
Combined death/reinfarction/recurrent ischemia/urgent revascularization and new presentation CHF and shock
Time frame: 30 days.
Major bleeding and hemorrhagic stroke
Time frame: 30 days
Combined death/reinfarction and combined revascularization/recurrent ischemia
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2009.
- Derived from this study: PubMed 26175478Abdel-Qadir H, Yan AT, Tan M, Borgia F, Piscione F, Di Mario C, Halvorsen S, Cantor WJ, Westerhout CM, Scheller B, Le May MR, Fernandez-Aviles F, Sanchez PL, Lee DS, Goodman SG. Consistency of benefit from an early invasive strategy after fibrinolysis: a patient-level meta-analysis. Heart. 2015 Oct;101(19):1554-61. doi: 10.1136/heartjnl-2015-307815. Epub 2015 Jul 14.
- Derived from this study: PubMed 25616922Madan M, Halvorsen S, Di Mario C, Tan M, Westerhout CM, Cantor WJ, Le May MR, Borgia F, Piscione F, Scheller B, Armstrong PW, Fernandez-Aviles F, Sanchez PL, Graham JJ, Yan AT, Goodman SG. Relationship between time to invasive assessment and clinical outcomes of patients undergoing an early invasive strategy after fibrinolysis for ST-segment elevation myocardial infarction: a patient-level analysis of the randomized early routine invasive clinical trials. JACC Cardiovasc Interv. 2015 Jan;8(1 Pt B):166-174. doi: 10.1016/j.jcin.2014.09.005. Epub 2014 Oct 31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myocardial Infarction, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Nov 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Carlo Di Mario, MD (0044 20 7351 ext. 8616, c.dimario@rbht.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined death/reinfarction (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01014182, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2009.