Trial Outcomes & Findings for REVEAL: Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (NCT NCT00378352)
NCT ID: NCT00378352
Last Updated: 2017-05-09
Results Overview
Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
223 participants
Primary outcome timeframe
performed 2 to 6 days after study medication administration (first CMR)
Results posted on
2017-05-09
Participant Flow
Conducted at 28 US sites between October 2006 and February 2010 and included 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy
Participant milestones
| Measure |
Dose Escalation 15,000 Units Epoetin Alfa
|
Dose Escalation 30,000 Units Epoetin Alfa
|
Dose Escalation 60,000 Units Epoetin Alfa
|
Dose Escalation Placebo
|
Efficacy Phase 60,000 Units Epoetin Alfa
Prospective, randomized, double-blind, placebo-controlled trial Single dose 60000 U of epoetin alfa
|
Efficacy Phase Placebo
Single dose placebo
|
|---|---|---|---|---|---|---|
|
Dose Escalation 15,000 Units
STARTED
|
20
|
0
|
0
|
11
|
0
|
0
|
|
Dose Escalation 15,000 Units
Safety Analysis
|
19
|
0
|
0
|
11
|
0
|
0
|
|
Dose Escalation 15,000 Units
COMPLETED
|
15
|
0
|
0
|
10
|
0
|
0
|
|
Dose Escalation 15,000 Units
NOT COMPLETED
|
5
|
0
|
0
|
1
|
0
|
0
|
|
Dose Escalation 30,000 Units
STARTED
|
0
|
19
|
0
|
11
|
0
|
0
|
|
Dose Escalation 30,000 Units
Safety Analysis
|
0
|
20
|
0
|
11
|
0
|
0
|
|
Dose Escalation 30,000 Units
COMPLETED
|
0
|
16
|
0
|
9
|
0
|
0
|
|
Dose Escalation 30,000 Units
NOT COMPLETED
|
0
|
3
|
0
|
2
|
0
|
0
|
|
Dose Escalation 60,000 Units
STARTED
|
0
|
0
|
20
|
11
|
0
|
0
|
|
Dose Escalation 60,000 Units
Safety Analysis
|
0
|
0
|
19
|
11
|
0
|
0
|
|
Dose Escalation 60,000 Units
COMPLETED
|
0
|
0
|
17
|
10
|
0
|
0
|
|
Dose Escalation 60,000 Units
NOT COMPLETED
|
0
|
0
|
3
|
1
|
0
|
0
|
|
Efficacy Phase
STARTED
|
0
|
0
|
0
|
0
|
65
|
66
|
|
Efficacy Phase
Safety Analysis
|
0
|
0
|
0
|
0
|
67
|
64
|
|
Efficacy Phase
COMPLETED
|
0
|
0
|
0
|
0
|
54
|
59
|
|
Efficacy Phase
NOT COMPLETED
|
0
|
0
|
0
|
0
|
11
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
REVEAL: Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction
Baseline characteristics by cohort
| Measure |
Epoetin Alfa
n=123 Participants
Dose escalation and efficacy phases
|
Placebo
n=99 Participants
Dose escalation and efficacy phases
|
Total
n=222 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.8 years
STANDARD_DEVIATION 12.4 • n=5 Participants
|
55.6 years
STANDARD_DEVIATION 12.5 • n=7 Participants
|
56 years
STANDARD_DEVIATION 12 • n=5 Participants
|
|
Age, Customized
Less than 70 years
|
103 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
184 Participants
n=5 Participants
|
|
Age, Customized
Greater than or equal to 70 years
|
20 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
100 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
178 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
123 participants
n=5 Participants
|
99 participants
n=7 Participants
|
222 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: performed 2 to 6 days after study medication administration (first CMR)Population: Analysis only performed on subjects who completed the CMR examination
Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging.
Outcome measures
| Measure |
Epoetin Alfa
n=68 Participants
Highest dose cohort (60,000 U of epoetin alfa)
|
Placebo
n=68 Participants
Placebo for the highest dose
|
|---|---|---|
|
Infarct Size in the Territory of the Infarct Related Artery
|
15.8 percentage of LV mass
Standard Deviation 10.3
|
15.0 percentage of LV mass
Standard Deviation 10.0
|
SECONDARY outcome
Timeframe: 12 ± 2 weeks after study medicationPopulation: Analysis only performed on subjects who completed the CMR examination
Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging.
Outcome measures
| Measure |
Epoetin Alfa
n=61 Participants
Highest dose cohort (60,000 U of epoetin alfa)
|
Placebo
n=63 Participants
Placebo for the highest dose
|
|---|---|---|
|
Infarct Size in the Territory of the Infarct Related Artery
|
10.6 percentage of LV mass
Standard Deviation 8.6
|
10.4 percentage of LV mass
Standard Deviation 7.6
|
SECONDARY outcome
Timeframe: 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)Population: Analysis only performed on subjects who completed this component of the CMR examination
Outcome measures
| Measure |
Epoetin Alfa
n=68 Participants
Highest dose cohort (60,000 U of epoetin alfa)
|
Placebo
n=70 Participants
Placebo for the highest dose
|
|---|---|---|
|
LV Ejection Fraction
First CMR
|
48.2 percent
Standard Deviation 9.1
|
48.9 percent
Standard Deviation 8.7
|
|
LV Ejection Fraction
Second CMR
|
52.5 percent
Standard Deviation 9.3
|
52.0 percent
Standard Deviation 8.8
|
SECONDARY outcome
Timeframe: 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)Population: Analysis only performed on subjects who completed this component of the CMR examination
Outcome measures
| Measure |
Epoetin Alfa
n=65 Participants
Highest dose cohort (60,000 U of epoetin alfa)
|
Placebo
n=68 Participants
Placebo for the highest dose
|
|---|---|---|
|
LV Volume Indexed to BSA
End systolic, First CMR
|
34.7 ml/m^2
Standard Deviation 14.7
|
32.6 ml/m^2
Standard Deviation 10.6
|
|
LV Volume Indexed to BSA
End systolic, Second CMR
|
34.1 ml/m^2
Standard Deviation 14.0
|
32.0 ml/m^2
Standard Deviation 11.7
|
|
LV Volume Indexed to BSA
End diastolic, First CMR
|
65.6 ml/m^2
Standard Deviation 18.2
|
63.4 ml/m^2
Standard Deviation 15.4
|
|
LV Volume Indexed to BSA
End diastolic, Second CMR
|
70.0 ml/m^2
Standard Deviation 17.1
|
66.6 ml/m^2
Standard Deviation 19.1
|
SECONDARY outcome
Timeframe: 2 to 6 days after study medication administration (first CMR) and 12 ± 2 weeks later (second CMR)Population: Analysis only performed on subjects who completed this component of the CMR examination
Outcome measures
| Measure |
Epoetin Alfa
n=68 Participants
Highest dose cohort (60,000 U of epoetin alfa)
|
Placebo
n=69 Participants
Placebo for the highest dose
|
|---|---|---|
|
LV Mass Indexed to BSA
First CMR
|
74.2 g/m^2
Standard Deviation 15.2
|
69.2 g/m^2
Standard Deviation 13.0
|
|
LV Mass Indexed to BSA
Second CMR
|
67.3 g/m^2
Standard Deviation 14.7
|
61.8 g/m^2
Standard Deviation 14.1
|
SECONDARY outcome
Timeframe: baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) daysOutcome measures
| Measure |
Epoetin Alfa
n=125 Participants
Highest dose cohort (60,000 U of epoetin alfa)
|
Placebo
n=97 Participants
Placebo for the highest dose
|
|---|---|---|
|
Vital Signs
SBP, baseline
|
129.7 mmHg
Standard Deviation 17.9
|
126.2 mmHg
Standard Deviation 18.7
|
|
Vital Signs
SBP at 24 hours
|
118.7 mmHg
Standard Deviation 19.1
|
112.9 mmHg
Standard Deviation 16.7
|
|
Vital Signs
SBP at 48 hours
|
114.3 mmHg
Standard Deviation 18.3
|
114.3 mmHg
Standard Deviation 16.3
|
|
Vital Signs
SBP, 14 days
|
119.2 mmHg
Standard Deviation 18.9
|
115.2 mmHg
Standard Deviation 14.3
|
|
Vital Signs
SBP, 30 days
|
117.4 mmHg
Standard Deviation 16.3
|
117.9 mmHg
Standard Deviation 16.5
|
|
Vital Signs
DBP, baseline
|
78.5 mmHg
Standard Deviation 12.7
|
75.8 mmHg
Standard Deviation 13.8
|
|
Vital Signs
DBP, 24 hours
|
70.5 mmHg
Standard Deviation 12.9
|
66.3 mmHg
Standard Deviation 11.0
|
|
Vital Signs
DBP, 48 hours
|
68.0 mmHg
Standard Deviation 11.5
|
67.9 mmHg
Standard Deviation 11.5
|
|
Vital Signs
DBP, 14 days
|
71.2 mmHg
Standard Deviation 10.9
|
69.2 mmHg
Standard Deviation 9.8
|
|
Vital Signs
DBP, 30 days
|
71.0 mmHg
Standard Deviation 10.3
|
71.3 mmHg
Standard Deviation 10.8
|
SECONDARY outcome
Timeframe: baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) daysOutcome measures
| Measure |
Epoetin Alfa
n=125 Participants
Highest dose cohort (60,000 U of epoetin alfa)
|
Placebo
n=97 Participants
Placebo for the highest dose
|
|---|---|---|
|
Hemoglobin Levels
Baseline
|
13.8 g/dL
Standard Deviation 1.4
|
13.6 g/dL
Standard Deviation 1.7
|
|
Hemoglobin Levels
24 hours
|
13.4 g/dL
Standard Deviation 1.5
|
13.1 g/dL
Standard Deviation 1.7
|
|
Hemoglobin Levels
48 hours
|
13.3 g/dL
Standard Deviation 1.7
|
13.1 g/dL
Standard Deviation 1.8
|
|
Hemoglobin Levels
14 days
|
14.1 g/dL
Standard Deviation 1.4
|
13.5 g/dL
Standard Deviation 1.5
|
|
Hemoglobin Levels
30 days
|
14.2 g/dL
Standard Deviation 1.4
|
13.7 g/dL
Standard Deviation 1.5
|
SECONDARY outcome
Timeframe: baseline, 24 hours, 48 hours, 14 (+/- 5) days, and 30 (+/- 5) daysOutcome measures
| Measure |
Epoetin Alfa
n=125 Participants
Highest dose cohort (60,000 U of epoetin alfa)
|
Placebo
n=97 Participants
Placebo for the highest dose
|
|---|---|---|
|
Reticulocyte Counts
Baseline
|
1.4 percentage of red blood cells
Standard Deviation 0.5
|
1.3 percentage of red blood cells
Standard Deviation 0.5
|
|
Reticulocyte Counts
24 hours
|
1.6 percentage of red blood cells
Standard Deviation 0.5
|
1.3 percentage of red blood cells
Standard Deviation 0.6
|
|
Reticulocyte Counts
48 hours
|
1.8 percentage of red blood cells
Standard Deviation 0.5
|
1.3 percentage of red blood cells
Standard Deviation 0.5
|
|
Reticulocyte Counts
14 days
|
1.4 percentage of red blood cells
Standard Deviation 0.6
|
1.4 percentage of red blood cells
Standard Deviation 0.8
|
|
Reticulocyte Counts
30 days
|
1.2 percentage of red blood cells
Standard Deviation 0.6
|
1.3 percentage of red blood cells
Standard Deviation 0.7
|
SECONDARY outcome
Timeframe: from randomization to second CMROutcome measures
| Measure |
Epoetin Alfa
n=125 Participants
Highest dose cohort (60,000 U of epoetin alfa)
|
Placebo
n=97 Participants
Placebo for the highest dose
|
|---|---|---|
|
Number of Participants With Clinical Events
Death
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinical Events
Recurrent myocardial infarction
|
2 Participants
|
0 Participants
|
|
Number of Participants With Clinical Events
Unstaged Percutaneous Coronary Intervention
|
6 Participants
|
0 Participants
|
|
Number of Participants With Clinical Events
Coronary Artery Bypass Graft
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinical Events
Stroke
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinical Events
Stent thrombosis
|
3 Participants
|
0 Participants
|
|
Number of Participants With Clinical Events
Left Ventricular thrombus
|
3 Participants
|
2 Participants
|
|
Number of Participants With Clinical Events
New or worsening Congestive Heart Failur
|
5 Participants
|
2 Participants
|
Adverse Events
Epoetin Alfa
Serious events: 25 serious events
Other events: 55 other events
Deaths: 0 deaths
Placebo
Serious events: 10 serious events
Other events: 36 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Epoetin Alfa
n=125 participants at risk
Patients who received active study medication
|
Placebo
n=97 participants at risk
Patients who received placebo
|
|---|---|---|
|
Cardiac disorders
Atrioventricular block
|
0.80%
1/125
|
0.00%
0/97
|
|
Cardiac disorders
Cardiac failure congestive
|
3.2%
4/125
|
2.1%
2/97
|
|
Cardiac disorders
Stent Thrombosis
|
2.4%
3/125 • Number of events 3
|
0.00%
0/97
|
|
Cardiac disorders
MI
|
1.6%
2/125 • Number of events 2
|
0.00%
0/97
|
|
Renal and urinary disorders
Renal Failure
|
0.80%
1/125 • Number of events 1
|
2.1%
2/97 • Number of events 2
|
|
Cardiac disorders
Stroke
|
0.80%
1/125 • Number of events 1
|
0.00%
0/97
|
|
Cardiac disorders
Death
|
0.80%
1/125 • Number of events 1
|
0.00%
0/97
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.80%
1/125
|
1.0%
1/97
|
|
Cardiac disorders
Angina unstable
|
1.6%
2/125
|
1.0%
1/97
|
|
Cardiac disorders
Atrial fibrillation
|
0.80%
1/125
|
0.00%
0/97
|
|
Cardiac disorders
Coronary disease
|
0.00%
0/125
|
1.0%
1/97
|
|
Cardiac disorders
Dressler's syndrome
|
0.80%
1/125
|
0.00%
0/97
|
|
Cardiac disorders
Intracardiac thrombus
|
2.4%
3/125
|
2.1%
2/97
|
|
Cardiac disorders
Ventricular fibrillation
|
0.80%
1/125
|
0.00%
0/97
|
|
Cardiac disorders
Ventricular tachycardia
|
0.80%
1/125
|
1.0%
1/97
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.80%
1/125
|
0.00%
0/97
|
|
General disorders
Heparin-induced thrombocytopenia
|
0.80%
1/125
|
0.00%
0/97
|
|
General disorders
Non-cardiac chest pain
|
3.2%
4/125
|
1.0%
1/97
|
|
Infections and infestations
Pneumonia
|
0.00%
0/125
|
1.0%
1/97
|
|
Infections and infestations
Septic shock
|
0.80%
1/125
|
0.00%
0/97
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/125
|
1.0%
1/97
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.80%
1/125
|
0.00%
0/97
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/125
|
1.0%
1/97
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.80%
1/125
|
0.00%
0/97
|
|
Renal and urinary disorders
Nephropathy toxic
|
0.00%
0/125
|
1.0%
1/97
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.80%
1/125
|
0.00%
0/97
|
Other adverse events
| Measure |
Epoetin Alfa
n=125 participants at risk
Patients who received active study medication
|
Placebo
n=97 participants at risk
Patients who received placebo
|
|---|---|---|
|
Cardiac disorders
Cardiac disorders
|
20.8%
26/125
|
13.4%
13/97
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
9.6%
12/125
|
6.2%
6/97
|
|
General disorders
General disorders and administration site conditions
|
12.0%
15/125
|
12.4%
12/97
|
|
Investigations
Investigations
|
7.2%
9/125
|
8.2%
8/97
|
|
Psychiatric disorders
Psychiatric disorders
|
8.0%
10/125
|
1.0%
1/97
|
|
Vascular disorders
Vascular disorders
|
7.2%
9/125
|
3.1%
3/97
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60