Clinical trial NCT00157261: Thrombolysis Using Tenecteplase (Metalyse®) in Cardiac Arrest - The TROICA Trial
Official title: A Prospective, Randomised, Double-blind, Placebo-controlled, International, Multicentre, Parallel-group Comparison Trial Evaluating the Efficacy and Safety of Tenecteplase During Cardiopulmonary Resuscitation as Compared With Standard Treatment in Patients Suffering From Out-of-hospital Cardiac Arrest of Presumed Cardiac Origin Thrombolysis in Cardiac Arrest (TROICA) Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Heart Arrest
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 1050
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The general aim of this study is to compare the efficacy and safety of tenecteplase to standard treatment during cardiopulmonary resuscitation in patients suffering from out-of-hospital cardiac arrest.

Detailed description: The trial is a prospective, international, multi-centre, randomised (1:1), double-blind, parallel group comparison conducted for investigating the efficacy and safety of tenecteplase and placebo in patients with cardiac arrest of presumed cardiac origin.

Approximately 1300 patients (two groups of 650 patients; tenecteplase or matching placebo) suffering from witnessed (by eye or ear) out-of-hospital cardiac arrest of presumed cardiac origin, who are treated with ALS-CPR will be randomised at approximately 40 study centres. Randomisation is done immediately after insertion of an IV line is established. Study drug application, as a single IV bolus over 5-10 seconds, should be done immediately after the first vasopressor application during the ALS-CPR procedure.

PCI facilities will be required at all participating sites, i.e. hospitals receiving patients.

Study Hypothesis:

The primary aim of the trial is to demonstrate superiority in the intent-to-treat analysis of tenecteplase over placebo with regard to primary endpoint as the incidence of 30-day survival (30daysurv).

Comparison(s):

Group A (experimental; fibrinolytic treatment) Tenecteplase, as a single IV bolus over 5-10 seconds, immediately after first vasopressor dosage during standardised ALS-CPR procedures according to the International CPR Guidelines.

Group B (reference) Placebo, as a single IV bolus over 5-10 seconds, immediately after first vasopressor dosage during standardised ALS-CPR procedures according to the International CPR Guidelines.

Eligibility criteria: Patients, indicated for pre-hospital ALS-CPR procedures\* must fulfil the following inclusion criteria:

* Age at least 18 years (known or estimated; no upper limit)
* Out-of-hospital cardiac arrest of presumed cardiac origin (including recurrent cardiac arrest(s) after initial ROSC)
* Witnessed (by eye and/or ear) cardiac arrest
* BLS-CPR started within 10 min of onset (known or estimated time) and may be performed for up to 10 min, followed by ALS-CPR - or ALS-CPR started within 10 min of onset (known or estimated time)

Subjects who meet any of the following criteria will be excluded from randomisation into the study:

* In-hospital cardiac arrest
* Cardiac arrest of presumed non-cardiac origin (e.g., drug overdose, carbon monoxide poisoning, drowning, hypothermia, exsanguination, electrocution, asphyxia, hypoxia, trauma, cerebrovascular accident)
* Obvious significant internal bleeding
* Known neurological impairment
* Known coagulation disorder
* Known pregnancy
* Known current participation in any other clinical study
* Known hypersensitivity to study medication
* Institutionalised subjects (e.g., prisoner)
* Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated

Primary outcomes:
measure: The primary endpoint of this study is the 30-day survival rate
timeFrame: 30 days
measure: The co-primary endpoint of this study is hospital admission
timeFrame: 30 days
Secondary outcomes:
measure: Return of spontaneous circulation (ROSC)
timeFrame: 30 days
measure: 24-hr survival
timeFrame: 24 hours
measure: Neurological and overall outcome at hospital discharge or at day 30, whichever came first
timeFrame: 30 days
measure: Symptomatic intracranial haemorrhage (ICH) up to hospital discharge or day 30, whichever came first
timeFrame: 30 days
measure: Major bleeds up to hospital discharge or day 30, whichever came first
timeFrame: 30 days
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Univ.-Klinik f. Anaesthesie Graz
city: Innsbruck
country: Austria
facility: Univ.-Klinik f. Anaesthesie u. Intensivmedizin
city: Salzburg
country: Austria
facility: LKH Salzburg, St. Johanns-Spital
city: Wien
country: Austria
facility: Univ.-Klinik f. Notfallmedizin
city: Antwerpen
country: Belgium
facility: Algemeen Ziekenhuis Antwerpen / Campus Stuivenberg
city: Brugge
country: Belgium
facility: AZ Sint-Jan AV
city: Bruxelles
country: Belgium
facility: CHU Saint-Pierre
city: Bruxelles
country: Belgium
facility: AZ VUB
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Kortrijk
country: Belgium
facility: AZ Groeningen
city: La Louvière
country: Belgium
facility: CHU de Tivoli
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Liège
country: Belgium
facility: CHR de la Citadelle
city: Namur
country: Belgium
facility: CHR de Namur
city: Besançon cedex
country: France
facility: Hôpital Jean Minjoz
city: Bobigny cedex
country: France
facility: Hôpital Avicenne
city: Creteil cedex
country: France
facility: Hôpital Henri Mondor
city: Le Chesnay
country: France
facility: Hôpital André Mignot
city: Lille cedex
country: France
facility: Hôpital Régional et Universitaire
city: Melun cedex
country: France
facility: Hôpital Marc Jacquet
city: Montpellier cedex 5
country: France
facility: Hôpital Lapeyronie
city: Paris cedex 15
country: France
facility: Hôpital Necker
city: Rouen cedex
country: France
facility: Hôpital Charles Nicolle
city: Toulouse cedex
country: France
facility: Hôpital Purpan
city: Voiron cedex
country: France
facility: Hôpital Pierre Bazin
city: Berlin
country: Germany
facility: Universitätsklinikum Benjamin Franklin
city: Berlin
country: Germany
facility: Humboldt-Klinikum
city: Berlin
country: Germany
facility: DRK Kliniken Westend
city: Bielefeld
country: Germany
facility: Städtische Kliniken Bielefeld gem. GmbH
city: Bochum
country: Germany
facility: Klinikum der Ruhr-Universität Bochum
city: Dortmund
country: Germany
facility: Knappschaftskrankenhaus Dortmund
city: Freiburg/Breisgau
country: Germany
facility: Chirurgische Universität Freiburg
city: Göttingen
country: Germany
facility: Georg-August Universität Göttingen
city: Halle/Saale
country: Germany
facility: Martin-Luther-Universität Halle
city: Heidelberg
country: Germany
facility: Universität Heidelberg
city: Jena
country: Germany
facility: Friedrich-Schiller Universität Jena
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Kiel
country: Germany
facility: Berufsfeuerwehr Kiel
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: München
country: Germany
facility: Klinikum rechts der Isar
city: Saarbrücken
country: Germany
facility: Klinikum Saarbrücken gGmbH
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Bergamo
country: Italy
facility: A. O. Ospedali Riuniti di Bergamo
city: Como
country: Italy
facility: Ospedale S. Anna
city: Genova
country: Italy
facility: A. O. Universitaria S. Martino
city: Monza
country: Italy
facility: A. O. San Gerardo di Monza
city: Pavia
country: Italy
facility: Policlinico S. Matteo
city: Varese
country: Italy
facility: Osp. di Circolo Fondazione Macchi
city: Bergen
country: Norway
facility: ICU, Haukeland Universitetssykehus
city: Fredrikstad
country: Norway
facility: ICU, Sykehuset Østfold Fredrikstad
city: Stavanger
country: Norway
facility: Akuttklinikken / NLA, Sentralsjukehuset i Rogaland
city: Tønsberg
country: Norway
facility: Pre Hospital Klinikk, Sykehuset i Vestfold Tønsberg
city: Almería
country: Spain
facility: Hospital de Torrecárdenas / ICU
city: Barcelona
country: Spain
facility: Hospital Clínico Provincial de BCN / Cardiology Service
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía / ICU
city: Granada
country: Spain
facility: Vírgen de las Nieves. Critical Care-Emergency Room
city: Jerez de la Frontera
country: Spain
facility: Hospital de Jerez de la Frontera / ICU
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos / Hemodynamics
city: Malaga
country: Spain
facility: Hospital Clínico Universitario Vírgen de la Victoria / ICU
city: Sevilla
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Vigo
country: Spain
facility: Complejo Hospitalario Universitario de Vigo / Cardiology
city: Zaragoza
country: Spain
facility: Hospital Clinico Univ. Lozano Blesa
city: Gävle
country: Sweden
facility: Anestesikliniken
city: Göteborg
country: Sweden
facility: Hjärt/Kärlforskn.enheten, Sahlgrenska Univ.sjh. Göteborg
city: Stockholm
country: Sweden
facility: Södersjukhuset
city: Örebro
country: Sweden
facility: Universitetssjukhuset
city: Lausanne
country: Switzerland
facility: Centre interdisciplinaire des urgences (CIU), CHUV BH 06-429
city: Lugano
country: Switzerland
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: B.I. Pharma GmbH & Co. KG
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References:
citation: Bottiger BW, Arntz HR, Chamberlain DA, Bluhmki E, Belmans A, Danays T, Carli PA, Adgey JA, Bode C, Wenzel V; TROICA Trial Investigators; European Resuscitation Council Study Group. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med. 2008 Dec 18;359(25):2651-62. doi: 10.1056/NEJMoa070570.