Thrombolysis Versus Primary Angioplasty for AMI in Elderly Patients (TRIANA)

• ClinicalTrials.gov Identifier: NCT00257309
• Recruitment Status: Terminated
• First Posted: November 22, 2005
• Results First Posted: January 19, 2017
• Last Update Posted: January 19, 2017
• Sponsor: Spanish Society of Cardiology
• Collaborators: Fondo de Investigacion Sanitaria; Sanofi; Cordis Corporation; Medtronic; Guidant Corporation; Boston Scientific Corporation
• Information provided by (Responsible Party): Héctor Bueno, Spanish Society of Cardiology

Study Description

Brief Summary:

General objective: To compare the efficacy and safety of primary angioplasty(PA) with that of thrombolytic therapy (TT) for the treatment of AMI in patients >=75 years old with ST-segment elevation or LBBB AMI <6 hours of evolution without contraindications for TT.

Hypothesis: The therapeutical strategy based on PA is superior to that based initially on TT in patients >=75 years old with AMI.

Participating Centers: 27 Spanish hospitals performing >50 PA/year. Primary Endpoint (PE): Incidence of the aggregate of death of any cause, reinfarction or disabling stroke at 30 days. There are also 7 secondary endpoints (SE).

Procedure: Diagnosis of inclusion/exclusion criteria --> Centralized randomization --> Treatment allocation to 1) TT with weight adjusted TNK + unfractionated heparin or 2) PA within 120 minutes. Estimated Sample size and recruitment time: 570 patients in 19 months. Follow-up: Blinded evaluation of events (PROBE regulations) specified in PE and SE at 30 days and 12 months. Quality control: 100% variable and follow-up review by external CRO. Safety Committee and Event Adjudication Committee formed by experts not participating in the study.

Condition or disease	Intervention/treatment	Phase
Acute Myocardial Infarction	Drug: Tenecteplase + UFH (+ clopidogrel, since 01/97); Procedure: Primary angioplasty	Phase 4

Detailed Description:

Hypothesis of the study. In patients of 75 or more years of age with AMI and ST-elevation or LBBB, the treatment strategy based on primary angioplasty is superior to the treatment strategy based on initial fibrinolytic therapy for reducing the incidence of death, re-infarction and disabling CVA at 30 days. This benefit is maintained at 12 months.

Objectives General objective of the study. To compare the efficacy and safety of primary angioplasty and fibrinolytic treatment in >=75 year-old patients with AMI eligible for fibrinolytic therapy in Spanish medical centers with an active program of primary angioplasty.

Primary end point: Incidence of the combined end point of all-cause death, re-infartion or disabling stroke at 30 days

Secondary end points:

• All-cause death at 30 days
• Incidence of the combined end point of all-cause death, disabling CVA or de novo heart failure at 30 days
• Incidence of recurrent ischemia requiring emergency catheterization in the first 30 days

• Cause of death at 30 days classified in three groups:

  1. Shock or heart (pump) failure
  2. Mechanical complications (ruptures) or electromechanical dissociation
  3. Other causes (including bleeding)
• Incidence of major bleeding during hospital admission
• All-cause mortality at 12 months
• Period of time elapsed until presentation of any of the composite of all-cause death, reinfarction or disabling CVA at 12 months
• Period of time elapsed until the presentation of any composite of all-cause death, reinfarction, disabling CVA or non-elective hospital readmission for cardiac causes (unstable angina, heart failure, non-elective coronary revascularization at 12 months.

TYPE AND DESIGN OF THE CLINICAL TRIAL Clinical trial status Phase IV trial Description of randomization process The treatment strategy will be determined by a centralized randomization process, using a telephone system. Eligible patients will be randomized to one of two (2) treatment arms: fibrinolytic treatment or primary angioplasty.

Control and design This is a randomized multicenter, open blind clinical trial designed to compare the efficacy and safety of primary angioplasty vs. thrombolytic treatment in >=75 year-old patients with AMI and ST-elevation or de novo LBBB, eligible for thrombolysis, admitted at Spanish medical centers that have an active primary angioplasty program, within the first 6 hours after symptom onset.

Masking techniques Being an open trial there are not masking techniques, nor will there be an emergency opening procedure of emergency codes.

Pre-inclusion / clearance period Not applicable

SUBJECT SELECTION Inclusion / exclusion criteria Subjects must be >=75 years of age with AMI and ST-elevation or de novo LBBB, eligible for thrombolytic therapy, admitted in any Spanish medical center in which there is an active primary angioplasty program within the first 6 hours after symptom onset.

Each patient must fulfill all inclusion criteria and none of the exclusion criteria.

Inclusion criteria:

1. Subjects of 75 or more years of age

2. Diagnosis of AMI: chest pain or any symptom of myocardial ischemia of, at least, 20 minutes of duration, not responding to nitrate therapy, an evolution period of less than 6 hours after symptom onset until randomization process, and, at least, one of the following alterations:

   1. ST-elevation >=2 mm in 2 or more precordial leads
   2. ST-elevation >=1 mm in 2 or more anterior leads
   3. Complete de novo (or probably de novo) left bundle branch block (LBBB)
3. Subject should be able to give informed consent prior to randomization process and should agree to fulfill all procedures described in the protocol, including follow-up after hospital discharge. A written consent signed by a close relative with witness is also acceptable.

Exclusion criteria:

1. Documented contraindication to the use of fibrinolytics. 1.1. Internal active bleeding or known history of hemorrhagic diathesis 1.2. History of previous CVA of any kind or at any time 1.3. Intracranial tumor, arteriovenous malformation, aneurysm or cerebral aneurysm repair 1.4. Major surgery, parenchymal biopsy, ocular surgery or severe traumatism in the 6 weeks prior to randomization 1.5. Unexplained puncture in a non-compressible vascular location in the last 24 hours prior to randomization 1.6. Confirmed arterial hypertension with a reliable measurement of systolic AP >180 mmHg or diastolic AP >110 mmHg 1.7. Known thrombocytopenia < 100.000 platelets/mL 1.8. Prolonged (>20 minutes) or traumatic cardiopulmonar resuscitation (CPR) in the 2 weeks prior to randomization 1.9. History or signs suggesting aortic dissection
2. Cardiogenic shock
3. Estimated door-to-needle time >120 minutes
4. Administration of fibrinolysis in the 14 days prior to randomization
5. Administration of any glycoprotein IIa/IIIb inhibitor in the 24 hours prior to randomization
6. Administration of any Low Molecular Weight Heparin (LMWH) in the 8 hours prior to randomization
7. Actual oral anticoagulant treatment
8. Suspected AMI secondary to occlusion of one lesion treated previously with a percutaneous coronary intervention (within the previous 30 days for angioplasty or conventional stent and within the previous 12 months for coated stents)
9. Dementia or acute confusional state at the time of randomization
10. Subject incapacity or unwillingness to give informed consent -at least, verbally
11. Known renal failure (basal creatinine> 2,5 mg/dl)
12. Reduced life expectancy (<12 months) due to advanced or terminal concomitant condition
13. Subject participation in another clinical trial (assessing a drug or a device) in the 30 days prior to randomization

Diagnostic criteria for the pathologies of the study

Patients with a diagnosis of AMI presenting with:

• Chest pain or any symptom of myocardial ischemia of, at least, 20 minutes of duration, not responding to nitrate therapy and an evolution period of less than 6 hours after symptom onset until randomization process, with, at least, one of the following alterations:
• ST-elevation >=2 mm in 2 or more precordial leads
• ST-elevation >=1 mm in 2 or more anterior leads
• Complete de novo (or probably de novo) left bundle branch block (LBBB)

Estimate of sample size For the following conditions: α = 0.05 (2 tailed), power: 80% (β = 0.20) and assuming a composite event incidence rate (death, reinfarction and disabling CVA) based on previous registries (21.7% in the fibrinolysis group and 12.8% in the PA group), a sample size of 282 patients per group is needed to demonstrate that difference (8.9% in absolute terms and 40% in relative terms). Assuming a loss to follow-up rate of 1%, the total number is 570 patients

Estimated loss of patients prior to randomization During a period of 3 months all patients meeting inclusion criteria who, for any reason, are not enrolled in the study will be included in a registry with an abbreviated CRF recording inclusion/exclusion criteria, the reason for non-enrollment and follow-up at 30 days and 12 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 266 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TRIANA: A Randomized Trial to Compare the Efficay and Safety of Thrombolysis With Primary Angioplasty as Initial Reperfusion Therapy in Older Patients (>= 75 Years Old) With Acute Myocardial Infarction
• Study Start Date: April 2005
• Actual Primary Completion Date: February 2008
• Actual Study Completion Date: December 2008

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Thrombolysis; Weight adjusted tenecteplase bolus + Unfrationated heparin	Drug: Tenecteplase + UFH (+ clopidogrel, since 01/97)
Active Comparator: Primary angioplasty; Primary angioplasty	Procedure: Primary angioplasty

Outcome Measures

Primary Outcome Measures :

1. Incidence of Death or Reinfarction or Disabling Stroke [ Time Frame: 30 days ]
   Incidence of all-cause death or myocardial reinfarction or disabling stroke
2. Death/Reinfarction/Disabling Stroke at 30 Days [ Time Frame: 30 days ]
   Incidence of Death or Reinfarction or Disabling Stroke at 30 days

Eligibility Criteria

• Ages Eligible for Study: 75 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA:

1. Subjects of 75 or more years of age

2. Diagnosis of AMI: chest pain or any symptom of myocardial ischemia of, at least, 20 minutes of duration, not responding to nitrate therapy, an evolution period of less than 6 hours after symptom onset until randomization process, and, at least, one of the following alterations:

   1. ST-elevation >=2 mm in 2 or more precordial leads
   2. ST-elevation >=1 mm in 2 or more anterior leads
   3. Complete de novo (or probably de novo) left bundle branch block (LBBB)
3. Subject should be able to give informed consent prior to randomization process and should agree to fulfill all procedures described in the protocol, including follow-up after hospital discharge. A written consent signed by a close relative with witness is also acceptable.

EXCLUSION CRITERIA:

1. Documented contraindication to the use of fibrinolytics. 1.1. Internal active bleeding or known history of hemorrhagic diathesis 1.2. History of previous CVA of any kind or at any time 1.3. Intracranial tumor, arteriovenous malformation, aneurysm or cerebral aneurysm repair 1.4. Major surgery, parenchymal biopsy, ocular surgery or severe traumatism in the 6 weeks prior to randomization 1.5. Unexplained puncture in a non-compressible vascular location in the last 24 hours prior to randomization 1.6. Confirmed arterial hypertension with a reliable measurement of systolic AP >180 mmHg or diastolic AP >110 mmHg 1.7. Known thrombocytopenia < 100.000 platelets/mL 1.8. Prolonged (>20 minutes) or traumatic cardiopulmonar resuscitation (CPR) in the 2 weeks prior to randomization 1.9. History or signs suggesting aortic dissection
2. Cardiogenic shock
3. Estimated door-to-needle time >120 minutes
4. Administration of fibrinolysis in the 14 days prior to randomization
5. Administration of any glycoprotein IIa/IIIb inhibitor in the 24 hours prior to randomization
6. Administration of any Low Molecular Weight Heparin (LMWH) in the 8 hours prior to randomization
7. Actual oral anticoagulant treatment
8. Suspected AMI secondary to occlusion of one lesion treated previously with a percutaneous coronary intervention (within the previous 30 days for angioplasty or conventional stent and within the previous 12 months for coated stents)
9. Dementia or acute confusional state at the time of randomization
10. Subject incapacity or unwillingness to give informed consent -at least, verbally
11. Known renal failure (basal creatinine> 2,5 mg/dl)
12. Reduced life expectancy (<12 months) due to advanced or terminal concomitant condition
13. Subject participation in another clinical trial (assessing a drug or a device) in the 30 days prior to randomization

Contacts and Locations

Locations

Spain

Hospital Universitario Central de Asturias

Oviedo, Asturias, Spain, 33006

Hospital Universitario Son Dureta

Palma de Mallorca, Baleares, Spain, 07003

Hospital Universitario de Bellvitge

Hospitalet de Llobregat, Barcelona, Spain, 08907

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, La Coruña, Spain, 15706

Complejo Hospitalario de León

Leon, León, Spain, 24010

Hospital Universitario "Virgen de la Victoria"

Malaga, Málaga, Spain, 29010

Hospital de Navarra

Pamplona, Navarra, Spain, 31008

Hospital Universitario de Canarias

La Laguna, Tenerife, Spain, 38320

Hospital de Cruces

Barakaldo, Vizcaya, Spain, 48903

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, 08025

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain, 08036

Hospital Universitario Virgen de las Nieves

Granada, Spain, 18012

Hospital Juan Ramón Jiménez

Huelva, Spain, 21005

Complejo Hospitalario Universitario "Juan Canalejo"

La Coruña, Spain, 15006

Hospital General Universitario "Gregorio Maranon"

Madrid, Spain, 28007

Hospital Clínico "San Carlos"

Madrid, Spain, 28040

Hospital 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario La Paz

Madrid, Spain, 28046

Hospital Universitario Marques de Valdecilla

Santander, Spain, 39008

Hospital Universitario Virgen Macarena

Sevilla, Spain, 41009

Complejo Hospitalario de Toledo Hospital Virgen de la Salud

Toledo, Spain, 45004

Consorcio Hospital General Universitario de Valencia

Valencia, Spain, 46014

Hospital Clínico Universitario de Valladolid

Valladolid, Spain, 47005

Sponsors and Collaborators

Spanish Society of Cardiology

Fondo de Investigacion Sanitaria

Sanofi

Cordis Corporation

Medtronic

Guidant Corporation

Boston Scientific Corporation

Investigators

• Principal Investigator: Hector Bueno, MD, PhD; Spanish Society of Cardiology (WG on Ischemic Heart Disease and CCUs)
• Principal Investigator: Rosa Ana Hernández-Antolín, MD; Spanish Society of Cardiology (WG on Interventional Cardiology)

More Information

Publications of Results:

Bueno H, Betriu A, Heras M, Alonso JJ, Cequier A, García EJ, López-Sendón JL, Macaya C, Hernández-Antolín R; TRIANA Investigators. Primary angioplasty vs. fibrinolysis in very old patients with acute myocardial infarction: TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) randomized trial and pooled analysis with previous studies. Eur Heart J. 2011 Jan;32(1):51-60. doi: 10.1093/eurheartj/ehq375. Epub 2010 Oct 22.

Other Publications:

Bardají A, Bueno H, Fernández-Ortiz A, Cequier A, Augé JM, Heras M. [Type of treatment and short-term outcome in elderly patients with acute myocardial infarction admitted to hospitals with a primary coronary angioplasty facility. The TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) Registry]. Rev Esp Cardiol. 2005 Apr;58(4):351-8. Spanish.

Cequier A, Bueno H, Augé JM, Bardají A, Fernández-Ortiz A, Heras M. [Characteristics and mortality following primary percutaneous coronary intervention for acute myocardial infarction in Spain. Results from the TRIANA 1 (TRatamiento del Infarto Agudo de miocardio eN Ancianos) Registry]. Rev Esp Cardiol. 2005 Apr;58(4):341-50. Spanish.

• Responsible Party: Héctor Bueno, (Past) President. WG on IHD, Spanish Society of Cardiology
• ClinicalTrials.gov Identifier: NCT00257309
• Other Study ID Numbers: EUDRACT 2004-001943-31; FIS PI042122
• First Posted: November 22, 2005
• Results First Posted: January 19, 2017
• Last Update Posted: January 19, 2017
• Last Verified: November 2016

Keywords provided by Héctor Bueno, Spanish Society of Cardiology:

Acute myocardial infarction; Elderly; Thrombolysis; Primary angioplasty; Randomized trial; Efficacy; Safety

Additional relevant MeSH terms:

Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Tenecteplase; Clopidogrel; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Fibrinolytic Agents; Fibrin Modulating Agents