Condition category
Circulatory System
Date applied
12/09/2005
Date assigned
12/09/2005
Last edited
21/12/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.diagram-zwolle.nl

Contact information

Type

Scientific

Primary contact

Dr J Klijn

ORCID ID

Contact details

Diagram B.V.
Van Nahuysplein 6
Zwolle
8011 NB
Netherlands
+31 (0)38 4262997
j.klijn@diagram-zwolle.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

On-TIME 2

Study hypothesis

Primary:
Upfront pre-treatment with a high bolus dosage of Tirofiban will result in a lower extent of residual ST segment deviation 1 hour after Primary Coronary Angioplasty for acute myocardial infarction, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).
Secondary:
1. Upfront pre-treatment with a high bolus dosage of Tirofiban will result in a higher incidence of TIMI 3 flow of the infarct related vessel (IRV) at initial angiography, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).
2. Upfront pre-treatment with a high bolus dosage of Tirofiban will result in a higher incidence of normal myocardial perfusion as assessed by Myocardial Blush Grade scoring on immediately after primary angioplasty, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).
3. Upfront pre-treatment with a high bolus dosage of Tirofiban will result in a smaller infarct size as assessed by a single cTnT measurement performed 48-72 hours after Primary Coronary Angioplasty for acute myocardial infarction, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).
4. Upfront pre-treatment with a high bolus dosage of Tirofiban will result in a lower incidence of the combined occurrence of death, recurrent MI, urgent TVR or thrombotic bailout at 30 days follow-up, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).
5. Upfront pre-treatment with a high bolus dosage of Tirofiban will not result in a higher incidence of major bleeding (according to the most recent TIMI criteria), compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).

Ethics approval

Approved by the central Medical Ethics Review Committee (METC) of the Isala Ziekenhuizen of Zwolle (Netherlands)

Study design

Multinational, multicenter, double-blind, placebo-controlled, randomised

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Not Specified

Patient information sheet

Condition

Acute myocardial infarction

Intervention

1. Pre-treatment with a high bolus dosage of Tirofiban (25 ìg/kg bolus)
2. No pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel)

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

To investigate the effect of upfront pre-treatment with a high bolus dosage of Tirofiban on the extent of residual ST segment deviation 1 hour after Primary Coronary Angioplasty for acute myocardial infarction, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).

Secondary outcome measures

1. To investigate the effect of upfront pre-treatment with a high bolus dosage of Tirofiban on the incidence of TIMI 3 flow of the infarct related vessel (IRV) at initial angiography, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).
2. To investigate the effect of upfront pre-treatment with a high bolus dosage of Tirofiban on the incidence of normal myocardial perfusion as assessed by Myocardial Blush Grade scoring immediately after primary angioplasty, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).
3. To investigate the effect of upfront pre-treatment with a high bolus dosage of Tirofiban on infarct size as assessed by a single cTnT measurement performed 48-72 hours after Primary Coronary Angioplasty for acute myocardial infarction, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).
4. To investigate the effect of upfront pre-treatment with a high bolus dosage of Tirofiban on the incidence of the combined occurrence of death, recurrent MI, urgent TVR, or thrombotic bailout at 30 days follow-up, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).
5. To investigate the effect of upfront pre-treatment with a high bolus dosage of Tirofiban on the incidence of major bleeding (according to the most recent TIMI criteria), compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel).

Overall trial start date

03/04/2004

Overall trial end date

01/01/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. Symptoms of acute myocardial infarction of more than 30 minutes
2. ST segment elevation of >1 mV in 2 adjacent ECG leads, with cumulative ST segment deviation of 6 mm or more
3. Ability to perform PCA within 6 hours after onset of symptoms

Participant type

Patient

Age group

Not Specified

Gender

Both

Target number of participants

950

Participant exclusion criteria

1. Patient with a contraindication to anticoagulation:
a. Present bleeding disorder including gastrointestinal bleeding, hematuria, or known presence of occult blood in the stool prior to randomisation
b. Systolic blood pressure persistently exceeding 200 mm Hg and/or diastolic blood pressure exceeding 110 mm Hg at time of enrolment
c. Recent (<6 mnd) Stroke or Transient Ischemic Attack
2. Patients with severe renal failure (hemodialysis)
3. Patient with recent (< 30 days) major surgery
Participation in another clinical study one year before enrolment

Recruitment start date

03/04/2004

Recruitment end date

01/01/2007

Locations

Countries of recruitment

Netherlands

Trial participating centre

Diagram B.V.
Zwolle
8011 NB
Netherlands

Sponsor information

Organisation

Diagram B.V. (Netherlands)

Sponsor details

Van Nahuysplein 6
Zwolle
8011 NB
Netherlands

Sponsor type

Industry

Website

Funders

Funder type

Industry

Funder name

Merck Sharp & Dohme BV (MSD) (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18707985
2. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20510211
3. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/22162050
4. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21744314

Publication citations

  1. Results

    Van't Hof AW, Ten Berg J, Heestermans T, Dill T, Funck RC, van Werkum W, Dambrink JH, Suryapranata H, van Houwelingen G, Ottervanger JP, Stella P, Giannitsis E, Hamm C, , Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial., Lancet, 2008, 372, 9638, 537-546, doi: 10.1016/S0140-6736(08)61235-0.

  2. Results

    ten Berg JM, van 't Hof AW, Dill T, Heestermans T, van Werkum JW, Mosterd A, van Houwelingen G, Koopmans PC, Stella PR, Boersma E, Hamm C, , Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome., J. Am. Coll. Cardiol., 2010, 55, 22, 2446-2455, doi: 10.1016/j.jacc.2009.11.091.

  3. Results

    Hermanides RS, van Werkum JW, Ottervanger JP, Breet NJ, Gosselink AT, van Houwelingen KG, Dambrink JH, Hamm C, ten Berg JM, van 't Hof AW, , The effect of pre-hospital glycoprotein IIb-IIIa inhibitors on angiographic outcome in STEMI patients who are candidates for primary PCI., Catheter Cardiovasc Interv, 2012, 79, 6, 956-964, doi: 10.1002/ccd.23165.

  4. Results

    Hermanides RS, van Houwelingen G, Ottervanger JP, de Boer MJ, Dill T, Hamm C, Stella PR, Boersma E, ten Berg JM, van 't Hof AW, , The impact of age on effects of pre-hospital initiation of high bolus dose of tirofiban before primary angioplasty for ST-elevation myocardial infarction., Cardiovasc Drugs Ther, 2011, 25, 4, 323-330, doi: 10.1007/s10557-011-6314-8.

Additional files

Editorial Notes