ERASE-MI: Safety and Efficacy Study of Adjunctive Antiplatelet Therapy Prior to Primary PCI in Patients With STEMI

• Sponsor: Portola Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00546260
• Collaborator: (none)
• Enrollment: 70
• Locations: 31
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Safety and efficacy of adjunctive antiplatelet therapy prior to primary percutaneous intervention (PCI) in patients with ST-Elevation Myocardial Infarction (STEMI)

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Drug: placebo; Drug: PRT060128 Potassium	Phase 2

Detailed Description

Patients with STEMI who are to undergo primary PCI will be randomized to an intravenous (iv) bolus of placebo vs. PRT060128 prior to angiography.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Trial to Evaluate Effect of Adjunctive Antiplatelet Therapy With Intravenous PRT060128, a Selective P2Y12-Receptor Inhibitor, Before Primary Percutaneous Intervention (PCI) in ST-Elevation Myocardial Infarction (STEMI) Patients
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 Placebo for each Dose cohort: 10, 20, 40, and 60 mg	Drug: placebo; administration of iv bolus prior to angiography
Experimental: 2 Experimental drug for each Dose cohort: 10, 20, 40, and 60 mg	Drug: PRT060128 Potassium; administration of iv bolus prior to angiography

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days [30 days]

   TIMI Major:Intracranial bleeding or a decrease in the hemoglobin concentration of 5g/dL or more, or 15% or greater decrease in hematocrit. TIMI Minor:Hemoglobin concentration decreased by 3g/dL (but <5g/dL) or the hematocrit decreased by 10-15%. GUSTO Severe/life threatening:Intracranial hemorrhage or bleeding that causes hemodynamic compromise requiring intervention. GUSTO Moderate:Bleeding that requires bloodtransfusion but does not lead to hemodynamic compromise requiring intervention. Stroke:New focal neurologic deficit that does not resolve within 24 hours.

Secondary Outcome Measures

1. Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI [Time for contrast to reach a standardized distal coronary landmark in the culprit vessel]

   This measure was used to assess flow in the epicardial artery. It is the number of cine frames required for contrast to reach a standardized distal coronary landmark in the culprit vessel and was to be counted using an electronic frame counter.

2. Percentage ST-segment Resolution Prior to PCI [Before primary PCI]

   The relative effect of PRT060128 on ST-segment measured after PCI and expressed as a percent of ST-Segment prior to PCI. This measure was used to evaluate the dethrombotic and early reperfusion effects of PRT060128 in STEMI.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Persistent ST elevation ≥ 1mm (≥ 0.1mV) in two contiguous limb leads OR ≥ 2 mm (≥ 0.2mV) in two contiguous precordial leads, AND chest pain ≥ 20 minutes with onset within 6 hours of hospital presentation.

Exclusion Criteria:

• Cardiogenic shock (systolic blood pressure < 90 mm Hg requiring vasopressor or hemodynamic support)

• Uncontrolled hypertension defined as any measured systolic blood pressure (SBP) > 180 mm Hg or diastolic blood pressure (DBP) ≥ 110 mm Hg after the time -- History or symptoms of a congenital or acquired bleeding disorder or vascular malformation.

• Recent gastrointestinal bleeding within the last 30 days.

• Known thrombocytopenia (platelet count < 100,000/mm3).

• Any treatment with a fibrinolytic agent within the last 7 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tallahassee Memorial Medical Center	Tallahassee	Florida	United States	32308
2	Iowa Heart Center	Des Moines	Iowa	United States	50314
3	University of Kentucky Hospital, Gill Heart Center	Lexington	Kentucky	United States	40536
4	Maine Medical Center	Portland	Maine	United States	04102
5	Washington Adventist Hospital	Takoma Park	Maryland	United States	20912
6	Henry Ford Hospital	Detroit	Michigan	United States	48202
7	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
8	St. Joseph Mercy - Oakland	Pontiac	Michigan	United States	48341
9	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
10	William Beaumont Hospital - Troy Cardiology	Troy	Michigan	United States	48085
11	Lindner Clinical Trial Center	Cincinnati	Ohio	United States	45219
12	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
13	The Heart Center	Kingsport	Tennessee	United States	37660
14	Foothills Hospital	Calgary	Alberta	Canada	T2N2T9
15	Royal Alexandria Hospital	Edmonton	Alberta	Canada	T5H3V7
16	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G2B7
17	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z1M9
18	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z1Y6
19	Victoria Heart Institute, Royal Jubilee Hospital	Victoria	British Columbia	Canada	V8R4R2
20	Atlantic Health Services	St. John	New Brunswick	Canada	E2L4L2
21	General Hospital - Heath Sciences Centre	St. John's	Newfoundland and Labrador	Canada	A1B3V6
22	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H3A7
23	Hamilton Health Sciences	Hamilton	Ontario	Canada	L8L2X2
24	London Health Sciences	London	Ontario	Canada	N6A5A5
25	Trillium Health Centre - Mississaugua	Mississauga	Ontario	Canada	L5B2P7
26	Soutlake Regional Health Centre	Newmarket	Ontario	Canada	L3Y2R2
27	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N3M5
28	Montreal Heart Institute	Montreal	Quebec	Canada	H1T1C8
29	Centre Hospitalier Universitaire de Montreal - Hotel Dieu	Montreal	Quebec	Canada	H2W1T8
30	Hospital du Sacre Coeur	Montreal	Quebec	Canada	H4N1C5
31	Regina General Hospital	Regina	Saskatchewan	Canada	S4P0W5

Sponsors and Collaborators

• Portola Pharmaceuticals

Investigators

• Principal Investigator: Matthew T. Roe, MD, MHS, Duke Clinical Research Institute
• Principal Investigator: Michael Gibson, MD, MS, PERFUSE Angiographic Core Laboratory and Data Coordinating Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00546260
• Other Study ID Numbers: 07-113
• First Posted: Oct 18, 2007
• Last Update Posted: Jan 25, 2011
• Last Verified: Dec 1, 2010

• Keywords provided by , ,: STEMI; ACS
• Additional relevant MeSH terms: Myocardial Infarction; Infarction

Study Results

Participant Flow

Arm/Group Title	Placebo	Experimental
Arm/Group Description	Placebo Comparator	Experimental Cohorts (10, 20, 40, 60 mg)
Period Title: Overall Study
STARTED	36	34
COMPLETED	28	32
NOT COMPLETED	8	2

Baseline Characteristics

Arm/Group Title	Placebo	Experimental	Total
Arm/Group Description	Placebo Comparator	Experimental Cohorts (10, 20, 40, 60 mg)	Total of all reporting groups
Overall Participants	36	34	70
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	36 100%	34 100%	70 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.6 (11.9)	57.8 (10.4)	55.6 (11.5)
Sex: Female, Male (Count of Participants)
Female	7 19.4%	5 14.7%	12 17.1%
Male	29 80.6%	29 85.3%	58 82.9%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days
Description	TIMI Major:Intracranial bleeding or a decrease in the hemoglobin concentration of 5g/dL or more, or 15% or greater decrease in hematocrit. TIMI Minor:Hemoglobin concentration decreased by 3g/dL (but <5g/dL) or the hematocrit decreased by 10-15%. GUSTO Severe/life threatening:Intracranial hemorrhage or bleeding that causes hemodynamic compromise requiring intervention. GUSTO Moderate:Bleeding that requires bloodtransfusion but does not lead to hemodynamic compromise requiring intervention. Stroke:New focal neurologic deficit that does not resolve within 24 hours.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

All subjects receiving some component of study drug (the "as-treated" population)

Arm/Group Title	Placebo	Experimental
Arm/Group Description	Placebo Comparator	Experimental Cohorts (10, 20, 40, 60 mg)
Measure Participants	36	34
Dose 10 mg	3 8.3%	2 5.9%
Dose 20 mg	1 2.8%	0 0%
Dose 40 mg	4 11.1%	4 11.8%
Dose 60 mg	3 8.3%	0 0%

2. Secondary Outcome

Title	Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI
Description	This measure was used to assess flow in the epicardial artery. It is the number of cine frames required for contrast to reach a standardized distal coronary landmark in the culprit vessel and was to be counted using an electronic frame counter.
Time Frame	Time for contrast to reach a standardized distal coronary landmark in the culprit vessel

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Placebo	Experimental
Arm/Group Description	Placebo Comparator	Experimental Cohorts (10, 20, 40, 60 mg)
Measure Participants	28	32
Dose 10 mg	42	59
Dose 20 mg	100	100
Dose 40 mg	100	100
Dose 60 mg	100	100

3. Secondary Outcome

Title	Percentage ST-segment Resolution Prior to PCI
Description	The relative effect of PRT060128 on ST-segment measured after PCI and expressed as a percent of ST-Segment prior to PCI. This measure was used to evaluate the dethrombotic and early reperfusion effects of PRT060128 in STEMI.
Time Frame	Before primary PCI

Outcome Measure Data

Analysis Population Description

Per protocol.

Arm/Group Title	Placebo	Experimental
Arm/Group Description	Placebo Comparator	Experimental Cohorts (10, 20, 40, 60 mg)
Measure Participants	28	32
Dose 10 mg	82.8	65
Dose 20 mg	72.4	86.5
Dose 40 mg	75.3	37.9
Dose 60 mg	77.6	71.5

Adverse Events

Arm/Group Title	Placebo		Experimental
Arm/Group Description	Placebo Comparator		Experimental Cohorts (10, 20, 40, 60 mg)
All Cause Mortality
	Placebo		Experimental
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Experimental
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/36 (22.2%)		2/34 (5.9%)
Cardiac disorders
Angina unstable	1/36 (2.8%)	1	0/34 (0%)	0
Cardiogenic shock	2/36 (5.6%)	2	0/34 (0%)	0
General disorders
Chest pain	2/36 (5.6%)	2	0/34 (0%)	0
Vessel puncture site haemorrhage	1/36 (2.8%)	1	0/34 (0%)	0
Injury, poisoning and procedural complications
Thrombosis in device	0/36 (0%)	0	1/34 (2.9%)	1
Metabolism and nutrition disorders
Diabetes mellitus	1/36 (2.8%)	1	0/34 (0%)	0
Nervous system disorders
Ischaemic stroke	0/36 (0%)	0	1/34 (2.9%)	1
Vascular disorders
Peripheral artery dissection	1/36 (2.8%)	1	0/34 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Experimental
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/36 (41.7%)		21/34 (61.8%)
Cardiac disorders
Bradycardia	1/36 (2.8%)	1	2/34 (5.9%)	2
Ventricular tachycardia	3/36 (8.3%)	3	3/34 (8.8%)	3
Gastrointestinal disorders
Nausea	0/36 (0%)	0	2/34 (5.9%)	2
General disorders
Pyrexia	0/36 (0%)	0	2/34 (5.9%)	2
Vessel puncture site haematoma	1/36 (2.8%)	1	2/34 (5.9%)	2
Vessel puncture site pain	3/36 (8.3%)	3	0/34 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/36 (0%)	0	2/34 (5.9%)	2
Nervous system disorders
Headache	1/36 (2.8%)	1	3/34 (8.8%)	3
Psychiatric disorders
Insomnia	0/36 (0%)	0	2/34 (5.9%)	2
Vascular disorders
Hypotension	6/36 (16.7%)	6	3/34 (8.8%)	3

Limitations/Caveats

Because Part II of the study was not completed and Part I had a small sample size, no conclusions could be drawn regarding efficacy.

More Information

Certain Agreements

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

Sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo. Additionally, individual publication may occur after coordinated multi-center publication.