Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX

STEMI Clinical Trial

— MATRIX  

Official title:

Phase IIIb Study Minimizing Adverse Haemmhorragic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01433627
• Other study ID #: RFBU 11-I
• Secondary ID: 2011-000430-11
• Status: Active, not recruiting
• Phase: Phase 3
• First received: September 12, 2011
• Last updated: January 28, 2015
• Start date: October 2011
• Est. completion date: December 2015

Study information

• Verified date: January 2015
• Source: Italian Society of Invasive Cardiology
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

This protocol describes a study to compare intended trans-radial versus trans-femoral intervention and bivalirudin monotherapy versus current European standard of care consisting of unfractionated heparin (UFH) plus provisional use of glycoprotein IIb/IIIa inhibition via the use of one of the three available agents on the market (e.g. abciximab, tirofiban or eptifibatide) in patients (≥18 years) with ACS, that are intended for an invasive management strategy. This study will be conducted in compliance with Good Clinical Practices (GCP) including the Declaration of Helsinki and all applicable regulatory requirements.

Description:

The use of combined antithrombotic therapies over the last two decades has decreased the risk of a heart attack after percutaneous coronary intervention substantially but has also been associated with a significant increase in bleeding risk. Therapies or strategies that maintain the benefits seen with currently available antithrombotic therapies but which have lower bleeding risk are therefore of great clinical importance. Indeed, major bleeding is currently the most common non-cardiac complication of therapy for patients with coronary artery disease who have undergone percutaneous coronary intervention (PCI).

Bleeding in patients with acute coronary syndrome (ACS) is associated with an increased risk of long term mortality and morbidity, and this relationship is currently thought to be causal. Therefore' reducing the frequency of bleeding events while maintaining efficacy is an important goal in the management of patients with ACS. The most common site of bleeding in invasively managed patients with ACS is at the femoral artery puncture site used for heart catheterization

The MATRIX study is a multi-centre, prospective, randomised, open-label, 2 by 2 factorial comparison of trans-radial vs. trans-femoral intervention and bivalirudin vs. unfractionated heparin and provisional use of glycoprotein IIb/IIIa inhibitor.

Objectives:

1. To demonstrate that trans-radial intervention as compared to femoral access site is associated to lower rate of the composite endpoint of death, MI or stroke within the first 30 days after randomization in acute coronary syndrome patients undergoing early invasive management.

2. To demonstrate that bivalirudin infusion as compared to standard of care therapy consisting of unfractionated heparin and provisional use of glycoprotein IIb/IIIa inhibitors are associated to lower rate of the composite endpoint of death, MI or stroke within the first 30 days after randomization in acute coronary syndrome patients undergoing early invasive management.

Patients randomly assigned to receive bivalirudin will be randomized to stop bivalirudin infusion at the end of PCI or to prolong bivalirudin at an infusion rate of 0.25 mg/kg/hour for at least 6 hours after completion of PCI. The primary hypothesis in this sub-randomization is that prolonged post-intervention bivalirudin infusion will be superior to no bivalirudin post-PCI infusion with respect to the net composite outcome consisting of any death, MI, stroke, urgent TVR, stent thrombosis and BARC-defined type 3 and 5 bleeding events within 30 days. Secondary objectives for the sub-randomization of prolonged bivalirudin versus no post-PCI infusion in the bivalirudin group will consist of each component of the primary composite endpoint through the entire follow-up duration

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 7200
• Est. completion date: December 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

NSTEACS definition: Patients with all of the following criteria will be eligible:

1. history consistent with new, or worsening ischemia, occurring at rest or with minimal activity;

2. enrollment within 7 days of the most recent symptoms;

3. planned coronary angiography with possible indication to PCI;

4. at least 2 of the following criteria: 1. Aged 60 years or older, 2. Troponin T or I or creatine kinase MB above the upper limit of normal; 3. Electrocardiograph changes compatible with ischemia, ie, ST depression of 1 mm or greater in 2 contiguous leads, T-wave inversion more than 3 mm, or any dynamic ST shifts;

STEMI definition: i) chest pain for >20 min with an electrocardiographic ST-segment elevation =1 mm in two or more contiguous electrocardiogram (ECG) leads, or with a new left bundle-branch block, or an infero-lateral myocardial infarction (MI) with ST segment depression of =1 mm in =2 of leads V1-3 with a positive terminal T wave and ii) admission either within 12 h of symptom onset or between 12 and 24 h after onset with evidence of continuing ischemia or previous lytic treatment.

Exclusion Criteria:

1. Patients who can not give informed consent or have a life expectancy of <30 days

2. Allergy/intolerance to Bivalirudin or unfractionated heparin.

3. Stable or silent CAD as indication to coronary angiography

4. Treatment with LWMH within the past 6 hours

5. Treatment with any GPI in the previous 3 days

6. Absolute contraindications or allergy that cannot be pre-medicated to iodinated contrast or to any of the study medications including aspirin or clopidogrel.

7. Contraindications to angiography, including but not limited to severe peripheral vascular disease.

8. If it is known pregnant or nursing mothers. Women of child-bearing age will be asked if they are pregnant or think that they may be pregnant.

9. If it is known a creatinine clearance <30 mL/min or dialysis dependent.

10. Previous enrollment in this study.

11. Treatment with other investigational drugs or devices within the 30 days preceding

12. Randomisation or planned use of other investigational drugs or devices in this trial.

13. Severe uncontrolled hypertension (defined as persistent systolic blood pressure higher than 220 mmHg despite medical treatment).

14. Subacute bacterial endocarditis

15. PCI in the previous 30 days

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Coronary Syndromes
• NSTEMI
• STEMI

Intervention

Other:
• trans-radial and short-term bivalirudin
trans-radial intervention followed by Bivalirudin given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI at which time the infusion should be stopped.
• trans-radial and long-term bivalirudin infusion
Trans-radial intervention: will be performed according to institutional guidelines and established local practice. Bivalirudin: given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI at which time the infusion should be reduced to a dose of 0.25 mg/kg/h for at least 6 hours. An optional higher-dose infusion of 1.75 mg/kg/h is also permitted for up to 4 hours in the prolonged infusion arm but prohibited in the short bivalirudin group.
• trans-radial and standard of care pharmacology
Unfractionated heparin (UFH) (100 IU/kg with no glycoprotein IIb/IIIa inhibitor (GPI) and 60 IU/kg with a GPI); +/- routine or bail out eptifibatide (two 180 µg /kg boluses with a 10 minute interval followed by an infusion of 2.0 µg /kg/min for 72-96 hours) or tirofiban (25 µg/kg followed by an infusion of 0.15 µg/kg/min for 18 to 24 hours) or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 µg/kg/min for 12-24 hours (maximum dose, 10 µg/min).
• Trans-femoral and Short-term bivalirudin
Trans-femoral intervention: will be performed according to institutional guidelines and established local practice. Access closure devices are allowed as per local practice. Bivalirudin will be given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI.
• trans-femoral and long-term bivalirudin infusion
Trans-femoral intervention: will be performed according to institutional guidelines and established local practice. Access closure devices are allowed as per local practice. Bivalirudin will be given immediately upon enrolment as bolus of 0.75 mg/kg followed immediately by an infusion of 1.75 mg/kg/h. This infusion should be run continuously until completion of PCI at which time the infusion should be reduced to a dose of 0.25 mg/kg/h for at least 6 hours. An optional higher-dose infusion of 1.75 mg/kg/h is also permitted for up to 4 hours in the prolonged infusion arm but prohibited in the short bivalirudin group.
• trans-femoral and standard of care pharmacology
Trans-femoral intervention: will be performed according to institutional guidelines and established local practice. Access closure devices are allowed as per local practice. Unfractionated heparin (UFH) (100 IU/kg with no glycoprotein IIb/IIIa inhibitor (GPI) and 60 IU/kg with a GPI); +/- routine or bail out eptifibatide (two 180 µg /kg boluses with a 10 minute interval followed by an infusion of 2.0 µg /kg/min for 72-96 hours) or tirofiban (25 µg/kg followed by an infusion of 0.15 µg/kg/min for 18 to 24 hours) or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 µg/kg/min for 12-24 hours (maximum dose, 10 µg/min).

Locations

Country	Name	City	State
Italy	P.O. Zona Aretina-Ospedale San Donato	Arezzo	Toscana
Italy	A.O. G. Mazzoni	Ascoli Piceno	Marche
Italy	Ospedale Di Venere - ASL Bari	Bari	Puglia
Italy	Policlinico Sant'Orsola Malpighi	Bologna	Emilia Romagna
Italy	Spedali Civili di Brescia	Brescia	Lombardia
Italy	Azienda USL Sirai	Carbonia	Sardegna
Italy	A. O. Universitaria Policlinico V. Emanuele Ferrarotto	Catania	Sicilia
Italy	Azienda Ospedaliera Pugliese Ciaccio - Catanzaro	Catanzaro	Calabria
Italy	Ospedale Clinicizzato SS Annunziata di Chieti	Chieti	Abruzzo
Italy	Azienda Ospedaliera Sant'Anna di Como	Como	Lombardia
Italy	Maria Cecilia Hospital	Cotignola	RA
Italy	Ospedale S. Croce e Carlo	Cuneo	Piemonte
Italy	Azienda Ospedaliera di Desio e Vimercate - P.O. di Desio	Desio	Lombardia
Italy	Ospedale Sacra Famiglia	Erba	Lombardia
Italy	Presidio Ospedaliero di Este	Este	Veneto
Italy	University Hospital of Ferrara	Ferrara	Emilia Romagna
Italy	Ospedale G. B. Morgagni	Forlì	Emilia Romagna
Italy	Azienda Ospedaliera Universitaria "San Martino"	Genova	Liguria
Italy	Ospedale Villa Scassi	Genova	Liguria
Italy	Azienda USL - Grosseto	Grosseto	Toscana
Italy	Ospedale Santa Maria Goretti	Latina	Lazio
Italy	Città di Lecce Ospedale (GVM)	Lecce	Puglia
Italy	Ospedale Vito Fazzi	Lecce	Puglia
Italy	Ospedale Mater Salutis di Legnago	Legnago	Veneto
Italy	Ospedale di Lodi	Lodi	Lombardia
Italy	Ospedale del Cuore "G. Pasquinucci" Massa	Massa Carrara	Toscana
Italy	A.O: Fatebenefratelli e oftalmico	Milano	Lombardia
Italy	Ospedale Civile di Mirano	Mirano	Veneto
Italy	A.O. AORN Cardarelli	Napoli	Campania
Italy	Azienda Ospedaliera Monaldi	Napoli	Campania
Italy	Policlinico Federico II	Napoli	Campania
Italy	Azienda Ospedaliero-Universitaria "Maggiore della Carità"	Novara	Piemonte
Italy	Ospedale San Francesco	Nuoro	Sardegna
Italy	A. O. Universitaria San Luigi Gonzaga di Orbassano	Orbassano	Piemonte
Italy	Villa Maria Eleonora Hospital	Palermo	Sicilia
Italy	Azienda Ospedaliera San Salvatore	Pesaro	Marche
Italy	Ospedale Civile Santo Spirito	Pescara	Abruzzo
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa	Toscana
Italy	Azienda S. Maria Nuova di Reggio Emilia	Reggio Emilia	Emilia Romagna
Italy	Ospedale degli Infermi	Rimini	Emilia Romagna
Italy	Ospedale degli Infermi	Rivoli	TO
Italy	A.O. Sandro Pertini	Roma	Lazio
Italy	Ospedale del Santo Spirito in Sassia	Roma	Lazio
Italy	Ospedale San Camillo di Roma	Roma	Lazio
Italy	Policlinico Casilino	Roma	Lazio
Italy	Università Campus Bio-Medico di Roma	Rome
Italy	Istituto Clinico Humanitas IRCCS	Rozzano	MI
Italy	IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Puglia
Italy	Ospedali Riuniti ASL 17	Savigliano	Piemonte
Italy	A.O. Civili Riuniti - Giovanni Paolo II	Sciacca	Sicily
Italy	IRCCS Multimedica	Sesto San Giovanni	Lombardia
Italy	Ospedale Umberto I di Siracusa	Siracusa	Sicilia
Italy	Ospedale S. Vincenzo	Taormina	Sicilia
Italy	Casa di Cura Villa Verde	Taranto	Puglia
Italy	A.O. Universitaria Molinette San Giovanni Battista	Torino	Piemonte
Italy	Ospedale San Giovanni Bosco	Torino	Piemonte
Italy	Presidio Ospedaliero Santa Chiara	Trento	Trentino Alto Adige
Italy	A.O. Treviglio	Treviglio	Lombardia
Italy	Azienda Ospedaliera Universitaria Ospedali Riuniti	Trieste	Friuli Venezia Giulia
Italy	Azienda Ospedaliera S. Maria della Misericordia di Udine	Udine	Friuli Venezia Giulia
Italy	A. O. Ospedale Civile di Vimercate	Vimercate	Lombardia
Italy	Policlinico San Marco	Zingonia	Lombardia

Sponsors (2)

Lead Sponsor	Collaborator
Italian Society of Invasive Cardiology	Eustrategy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the composite of Death, non-fatal myocardial infarction or stroke	To demonstrate in ACS patients undergoing an early invasive management, i.e. diagnostic coronary angiogram+PCI or ad hoc planned PCI that trans-radial intervention as compared to femoral access site is associated to lower rate of the composite endpoint of death, MI or stroke within the first 30 days after randomization.	30 days	Yes
Primary	The composite of death, non-fatal myocardial infarction or stroke	To demonstrate that in an ACS patients with an intended PCI treatment strategy or in whom upstream treatment was felt necessary by local investigators the use of bivalirudin as compared to unfractionated heparin (UFH) plus or minus Glycoprotein IIb/IIIa inhibitor (GPI) is associated to lower rate of the composite endpoint of death, MI or stroke within the first 30 days after randomization.	30 days	Yes
Primary	Death, non-fatal myocardial infarction, stroke, stent thrombosis or BARC-defined type 3 or 5 bleedings	The primary hypothesis of this sub-randomization is that prolonged post-intervention bivalirudin infusion (long bivalirudin arm) will be superior to peri-PCI bivalirudin infusion only (short bivalirudin arm) with respect to the net composite outcomes consisting of any death, MI, stroke, stent thrombosis or BARC-defined type 3 and 5 bleeding events within 30 days.	30 days	Yes
Secondary	the composite endpoint of death, MI, stroke or BARC-defined type 3 and 5 major bleeding complications	Key secondary objective: To demonstrate that trans-radial intervention as compared to femoral access site is associated to lower rate of the composite endpoint of death, MI, stroke or BARC-defined type 3 and 5 major bleeding complications within the first 30 days after randomization.	30 days	Yes
Secondary	Death, non-fatal MI, stroke or BARC-defined type 3 and 5 major bleeding	To demonstrate that use of bivalirudin as compared to unfractionated heparin (UFH) plus or minus Glycoprotein IIb/IIIa inhibitor (GPI) is associated to lower rate of the composite endpoint of death, MI, stroke or BARC-defined type 3 and 5 major bleeding complications within the first 30 days after randomization.	30 days	Yes