HEAT-PPCI: How Effective Are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention

• Sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust (Other)
• Overall Status: Completed
• CT.gov ID: NCT01519518
• Collaborator: (none)
• Enrollment: 1,829
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 83.2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare unfractionated heparin (UFH) and bivalirudin in the performance and subsequent outcomes of Primary percutaneous coronary intervention. This will be a pragmatic trial. Interventional procedures will be performed to reflect current and evolving standards, including predominant radial access. All patients will be treated with routine oral anti-platelet therapy pre-procedure. GP IIb/IIIa inhibitors will be reserved for 'bail out' treatment only.

Condition or Disease	Intervention/Treatment	Phase
Acute ST Elevation Myocardial Infarction	Drug: unfractionated heparin; Drug: Bivalirudin	Phase 4

Detailed Description

HEAT-PPCI is a single-centre prospective, dual-arm, open-label, randomised controlled trial comparing two antithrombotic agents in patients undergoing PPCI. All patients presenting to the PPCI service at Liverpool Heart and Chest Hospital will be assessed for trial eligibility. The patients will be allocated by randomisation in equal proportions to the two treatment groups receiving UFH (70 units/kg prior to the procedure) or bivalirudin (bolus of 0.75 mg/kg prior to the start of the intervention, followed by an infusion of 1.75 mg/kg per hour for the duration of the procedure).

Pre-Specified Subgroup Analyses

• Subgroup analyses looking at the impact of access site comparing radial versus femoral route

• Assessment of the outcomes in diabetic patients receiving oral hypoglycaemic or insulin therapy versus all other patients

• Comparing the outcomes in patients < or ≥ 75 years of age

• Type of p2y12 receptor inhibiting antiplatelet agent (Examples: clopidogrel, prasugrel, ticagrelor)

• Patients with impaired LV function versus normal LV function

• Patients managed with actual or attempted primary PCI versus no immediate PCI procedure attempted

PLATELET FUNCTION SUBSTUDY A substudy will be performed to assess indices of coagulation and platelet function studies comparing the impact of heparin or bivalirudin therapy on coagulation status at the end of the PPCI procedure. This study will be performed on all patients treated between the hours of 0800 and 1600, Monday to Friday. A single blood sample taken at the time of general blood sampling for routine clinical screening will be analysed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1829 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised Controlled Trial to Compare Unfractionated Heparin Versus Bivalirudin in the Treatment of Patients With a Clinical Diagnosis of ST-Segment Elevation Myocardial Infarction Events - For Planned Management With Primary PCI
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Unfractionated heparin 70 units/kg body weight intravenous	Drug: unfractionated heparin; 70 units/kg body weight intravenous; Other Names: UFH
Active Comparator: bivalirudin intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour	Drug: Bivalirudin; intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour; Other Names: Angiox

Outcome Measures

Primary Outcome Measures

1. Major Adverse Cardiac Events (MACE) in Terms of the Incidence of All Cause Mortality, Cerebrovascular Accident, Re-infarction and Additional Unplanned Target Lesion Revascularization [28 days]

2. Type 3-5 Bleeding According to BARC (Bleeding Academic Research Consortium)Definition [28 days]

Secondary Outcome Measures

1. CKMB Release Following Index Revascularisation Measured With a Single Estimation 12-18 Hours After the Procedure [28 days]

2. Minor Bleeding: Type 2 Bleeding According to BARC (Bleeding Academic Research Consortium) Definition [28 days]

3. Stent Thrombosis Rate (ARC Definite or Probable) [28 days]

4. For Illustration, and to Allow Comparison With Existing Trials the Rate of Net Adverse Clinical Events (NACE), Combining the Primary Safety and Efficacy Outcomes [28 days]

5. All Cause Mortality [1 year]

6. Development of Thrombocytopenia [28 days]

7. Door-to-first Device Time [28 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All patients presenting with a suspected myocardial infarction event with PPCI as the proposed index reperfusion strategy will be included in the trial

Exclusion Criteria:

• ≤ 18 years of age

• Known intolerance, hypersensitivity or contraindication to any trial medication

• Active bleeding at presentation

• Artificial ventilation, reduced conscious level or other factors precluding the administration of oral antiplatelet therapy

• Previous enrolment in this trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Liverpool Heart and Chest Hospital	Liverpool	Merseyside	United Kingdom	L14 3PE

Sponsors and Collaborators

• Liverpool Heart and Chest Hospital NHS Foundation Trust

Investigators

• Principal Investigator: Rod Stables, MA DM FRCP, Liverpool Heart and Chest Hospital, Liverpool, UK

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr Rod Stables, Consultant Cardiologist, Liverpool Heart and Chest Hospital NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT01519518
• Other Study ID Numbers: 923
• First Posted: Jan 27, 2012
• Last Update Posted: May 13, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Dr Rod Stables, Consultant Cardiologist, Liverpool Heart and Chest Hospital NHS Foundation Trust: ST elevation myocardial infarction; Primary percutaneous coronary intervention; Unfractionated heparin; Bivalirudin; primary angioplasty
• Additional relevant MeSH terms: Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction; Heparin; Calcium heparin; Bivalirudin

Study Results

Participant Flow

Arm/Group Title	Unfractionated Heparin	Bivalirudin
Arm/Group Description	70 units/kg body weight intravenous unfractionated heparin: 70 units/kg body weight intravenous	intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour Bivalirudin: intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour
Period Title: Overall Study
STARTED	914	915
COMPLETED	907	905
NOT COMPLETED	7	10

Baseline Characteristics

Arm/Group Title	Unfractionated Heparin	Bivalirudin	Total
Arm/Group Description	70 units/kg body weight intravenous unfractionated heparin: 70 units/kg body weight intravenous	intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour Bivalirudin: intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour	Total of all reporting groups
Overall Participants	907	905	1812
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	63.6	62.9	63.2
Sex: Female, Male (Count of Participants)
Female	244 26.9%	258 28.5%	502 27.7%
Male	663 73.1%	647 71.5%	1310 72.3%

Outcome Measures

1. Primary Outcome

Title	Major Adverse Cardiac Events (MACE) in Terms of the Incidence of All Cause Mortality, Cerebrovascular Accident, Re-infarction and Additional Unplanned Target Lesion Revascularization
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Bivalirudin
Arm/Group Description	70 units/kg body weight intravenous unfractionated heparin: 70 units/kg body weight intravenous	intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour Bivalirudin: intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour
Measure Participants	907	905
Number [percentage of total participants]	5.7 0.6%	8.7 1%

2. Primary Outcome

Title	Type 3-5 Bleeding According to BARC (Bleeding Academic Research Consortium)Definition
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Bivalirudin
Arm/Group Description	70 units/kg body weight intravenous unfractionated heparin: 70 units/kg body weight intravenous	intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour Bivalirudin: intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour
Measure Participants	907	905
Number [percentage of total participants]	3.1 0.3%	3.5 0.4%

3. Secondary Outcome

Title	CKMB Release Following Index Revascularisation Measured With a Single Estimation 12-18 Hours After the Procedure
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Minor Bleeding: Type 2 Bleeding According to BARC (Bleeding Academic Research Consortium) Definition
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Bivalirudin
Arm/Group Description	70 units/kg body weight intravenous unfractionated heparin: 70 units/kg body weight intravenous	intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour Bivalirudin: intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour
Measure Participants	907	905
Number [percentage of total participants]	10.8 1.2%	9.2 1%

5. Secondary Outcome

Title	Stent Thrombosis Rate (ARC Definite or Probable)
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Bivalirudin
Arm/Group Description	70 units/kg body weight intravenous unfractionated heparin: 70 units/kg body weight intravenous	intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour Bivalirudin: intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour
Measure Participants	907	905
Number [percentage of total participants]	0.9 0.1%	3.4 0.4%

6. Secondary Outcome

Title	For Illustration, and to Allow Comparison With Existing Trials the Rate of Net Adverse Clinical Events (NACE), Combining the Primary Safety and Efficacy Outcomes
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	All Cause Mortality
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Development of Thrombocytopenia
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Door-to-first Device Time
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Unfractionated Heparin		Bivalirudin
Arm/Group Description	70 units/kg body weight intravenous unfractionated heparin: 70 units/kg body weight intravenous		intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour Bivalirudin: intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour
All Cause Mortality
	Unfractionated Heparin		Bivalirudin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Unfractionated Heparin		Bivalirudin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Unfractionated Heparin		Bivalirudin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.