Safety of High-dose Tirofiban During Coronary Angioplasty (SANTISS)

February 1, 2011 updated by: S. Anna Hospital

Safety of High-dose Tirofiban in Patient Undergoing Coronary Angioplasty.

This single-centre study is intended to retrospectively check the safety of high-dose bolus of tirofiban in patients who underwent percutaneous angioplasty.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background The acute occlusion due to intrastent thrombosis represented a major event causing acute myocardial infarction, cardiac death and necessity for a new procedure or coronary by-pass intervention.

To avoid such complications different high anticoagulation regimens (heparin, antiplatelets agents and warfarin) were employed. Even if effective, such treatments were accompanied by a higher cost of side effects due to major bleeding (hemorrhagic stroke, retroperitoneal bleeding, gastrointestinal bleeding, need for transfusion, site access complications).

Pre-treatment with aspirin and ticlopidine was found to be very effective reducing intrastent acute thrombosis. Since several days of pre-treatment were required it became a limiting factor for interventional procedures forcing physicians to adopt a two-stage strategy that separated the diagnostic from interventional time increasing the hospital's costs and the patient's risks.

Beside that, high doses of heparin were still required during the procedures. The introduction of GP IIb/IIIa inhibitors was initially reserved to acute coronary syndrome, later it was shown how they reduce the composite incidence of death, myocardial infarction and the need for target vessel revascularization after percutaneous coronary intervention.

As major benefits arising from the use of those drugs, interventional procedures could be carried out at end of diagnostic procedure and major bleedings were reduced as require a lower heparin regimen.

Nowadays the most recent guidelines for the management of patients with acute coronary syndrome strongly recommend the use of IIb/IIIa inhibitors when percutaneous coronary intervention is performed. Although several randomized trials with different IIb/IIIa inhibitors have demonstrated the usefulness of this therapeutic strategy a number of unsolved issues concerning which agent should be used and most appropriate timing and dosage remain to be explored.

The use of tirofiban (10µ/Kg bolus followed by a 0.15µ/Kg/min infusion) during PCI has been evaluated with controversial results. The TARGET trial showed that tirofiban provides a significantly less protection during PCI than abciximab, and the RESTORE trial found that tirofiban did not significantly reduce the combined endpoint in comparison with heparin alone. The sub-therapeutic inhibition of GP IIb/IIIa binding activity has been invoked, in the first hour of tirofiban treatment, as plausible explanation, in fact with a 10µ/Kg bolus as employed in the TARGET study about 60% of platelet inhibition was achieved in the first hour.

Schneider first proposed an high dose bolus (25µ/Kg bolus followed by a 0.15µ/Kg/min 18-h infusion) to improve the efficacy of tirofiban during percutaneous coronary interventions and the extent of average inhibition increased during first hour to 95% that is similar with that achieved by abciximab. This observation was followed by several papers (with short series of patients) comparing the efficacy and safety of high dose bolus of tirofiban and abciximab that showed similar efficacy for both IIb-IIIa inhibitors.

Among those the works of Danzi (Brescia I), Bolognese (EVEREST sudy ) (Arezzo I) and Gunasekara (Brisbane Au). In all these studies the number of enrolled patients was slightly enough to compare tirofiban and abciximab for their efficacy but it is still uncertain if high dose bolus of tirofiban could suffer of major side effects due to bleeding. Even if in all those studies the safety of high dose bolus of tirofiban was disclaimed, the study populations were too small for conclusive data. Actually no data are available in the literature on larger series of patients treated with high dose bolus of tirofiban.

S. Anna Hospital Report After the preliminary results showing a similar effect using abciximab and high dose bolus of tirofiban, from September 2002, we started high dose regimen of tirofiban with good therapeutic result and no evidence of major side effects. Since January 2003 high dose bolus of tirofiban was then adopted as routine regimen for all patients undergoing to percutaneous coronary interventions considering that treatment as having the best efficacy to cost ratio.

The data of all those patients (about 2000) were collected in our files and could be retrieved for a safety study with regard to the major side effect.

Study Endpoints

The primary endpoint is mortality. Secondary endpoints are: incidence of major bleeding and the rate of site access complication. Major bleeding is defined as cerebrovascular, (emorrhagic stroke), retroperitoneal bleeding, gastrointestinal bleeding, need for transfusion. Site access complications is defined as pseudoaneurysm, arteriovenous fistula, major hematoma (decrease in hematocrit level more than 15%) and need for surgical repair. Sub-groups of patients referred to our institution to perform a rescue-PCI few hours after thrombolyses failure and treated with high dose bolus of tirofiban will be also be investigated as patient with high-risk of bleeding side effects.

Postdischarge clinical outcomes were ascertained by means of a hospital visit or information collected through the referring cardiologist.

Statistical Analysis

Data obtained from about 2000 patient's files will be written on a dedicated data form and then they will be collected by means of a friendly user, dedicated program, compiled for that study and then exported in a data file that will be analysed by BMDP package.

Continuous variables are expressed as mean value ± SD, and discrete variables are expressed as absolute values and percentages. Clinical and instrumental variables will be compared using the Student's t-, chi square and Fisher's exact test. For groups and and subgroups analise of variance as well logistic regression will be performed. P values of <0.05 will be considered statistically significant.

We planned to perform random controls to check the quality of data collection and interinal analyse when 500th patient's data will be collected.

We think that even with the limitations of a retrospective study, such an investigation may be of high interest and thus set the base, for future, to collect and perform a prospective analyse of our data, in comparison (or in random allocation, with a 3 to 1 design) with different agent(s).

Study Type

Interventional

Enrollment (Actual)

2000

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Catanzaro, Italy, 88100
        • S Anna Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients undergoing percutaneous coronary angioplasty

Exclusion Criteria:

  • Known allergy to tirofiban

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: A
Tirofiban
Drug: tirofiban
tirofiban high dose bolus 25µ/Kg
Other Names:
  • Aggrastat
Placebo Comparator: B
Clopidogrel
Drug: Clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Measure: all cause mortality
Time Frame: one year
one year

Secondary Outcome Measures

Outcome Measure
Time Frame
measure: major bleeding
Time Frame: one year
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

S. Anna Hospital

Investigators

  • Principal Investigator: Michele Schiariti, MD, University of Roma La Sapienza

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

November 30, 2007

First Submitted That Met QC Criteria

November 30, 2007

First Posted (Estimate)

December 4, 2007

Study Record Updates

Last Update Posted (Estimate)

February 2, 2011

Last Update Submitted That Met QC Criteria

February 1, 2011

Last Verified

February 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHA-1-2007

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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