Trial Outcomes & Findings for Efficacy and Safety of Aliskiren and Valsartan Versus Placebo in Patients Stabilized Following an Acute Coronary Syndrome (NCT NCT00409578)

Last Updated: 2011-04-19

Results Overview

Blood samples for the measurement of NT-proBNP were collected, processed, and shipped to the TIMI Biomarker Core Laboratory, Boston MA for storage and analysis. The change from baseline to Week 8 was expressed as the geometric mean of the ratio: Week 8/Baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

1101 participants

Primary outcome timeframe

Baseline to Week 8

Results posted on

2011-04-19

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo tablets and capsules	Aliskiren 300 mg Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.	Valsartan 320 mg Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.	Aliskiren/Valsartan 300/320 mg Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.
Overall Study STARTED	280	271	269	281
Overall Study COMPLETED	228	201	215	214
Overall Study NOT COMPLETED	52	70	54	67

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo tablets and capsules	Aliskiren 300 mg Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.	Valsartan 320 mg Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.	Aliskiren/Valsartan 300/320 mg Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.
Overall Study Adverse Event	27	37	25	33
Overall Study Abnormal laboratory value(s)	2	2	2	4
Overall Study Lack of Efficacy	0	0	0	2
Overall Study Subject no longer requires study drug	0	0	0	1
Overall Study Withdrawal by Subject	8	15	16	17
Overall Study Lost to Follow-up	2	0	2	2
Overall Study Administrative problems	8	9	2	4
Overall Study Death	2	4	4	2
Overall Study Protocol Violation	3	2	3	1
Overall Study Missing	0	1	0	1

Baseline Characteristics

Efficacy and Safety of Aliskiren and Valsartan Versus Placebo in Patients Stabilized Following an Acute Coronary Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=280 Participants Placebo tablets and capsules	Aliskiren 300 mg n=271 Participants Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.	Valsartan 320 mg n=269 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.	Aliskiren/Valsartan 300/320 mg n=281 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.	Total n=1101 Participants Total of all reporting groups
Age Continuous	63 years STANDARD_DEVIATION 11.8 • n=5 Participants	63 years STANDARD_DEVIATION 11.7 • n=7 Participants	64 years STANDARD_DEVIATION 11.6 • n=5 Participants	63 years STANDARD_DEVIATION 11.1 • n=4 Participants	63 years STANDARD_DEVIATION 11.6 • n=21 Participants
Sex: Female, Male Female	103 Participants n=5 Participants	86 Participants n=7 Participants	72 Participants n=5 Participants	87 Participants n=4 Participants	348 Participants n=21 Participants
Sex: Female, Male Male	177 Participants n=5 Participants	185 Participants n=7 Participants	197 Participants n=5 Participants	194 Participants n=4 Participants	753 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to Week 8

Population: Full analysis set: All patients who were correctly randomized. Missing baseline values were not imputed. The last post-baseline biomarker measurement collected was used for analysis. In the aliskiren treated group, 4 patients never received study drug but were included in the full analysis set but were not included in any efficacy analyses.

Outcome measures

Outcome measures
Measure	Placebo n=259 Participants Placebo tablets and capsules	Aliskiren 300 mg n=235 Participants Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.	Valsartan 320 mg n=246 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.	Aliskiren/Valsartan 300/320 mg n=256 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.
Change From Baseline in N-terminal proB-type Natriuretic Peptide (NT-proBNP) at Week 8	0.582 pg/mL Interval 0.502 to 0.676	0.563 pg/mL Interval 0.483 to 0.656	0.614 pg/mL Interval 0.526 to 0.716	0.635 pg/mL Interval 0.548 to 0.737

SECONDARY outcome

Timeframe: Baseline to Week 8

Blood samples for the measurement of BNP were collected, processed, and shipped to the TIMI Biomarker Core Laboratory, Boston MA for storage and analysis. The change from baseline to Week 8 was expressed as the geometric mean of the ratio: Week 8/Baseline.

Outcome measures

Outcome measures
Measure	Placebo n=252 Participants Placebo tablets and capsules	Aliskiren 300 mg n=229 Participants Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.	Valsartan 320 mg n=237 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.	Aliskiren/Valsartan 300/320 mg n=252 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.
Change From Baseline in B-type Natriuretic Peptide (BNP) at Week 8	0.642 pg/mL Interval 0.535 to 0.77	0.597 pg/mL Interval 0.495 to 0.72	0.670 pg/mL Interval 0.554 to 0.81	0.682 pg/mL Interval 0.568 to 0.818

SECONDARY outcome

Timeframe: Baseline to Week 8

A cardiac event was defined as at least one of the following events: Cardiovascular death, recurrent myocardial infarction (MI), or hospitalization for congestive heart failure (CHF), all to be confirmed by adjudication.

Outcome measures

Outcome measures
Measure	Placebo n=278 Participants Placebo tablets and capsules	Aliskiren 300 mg n=268 Participants Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.	Valsartan 320 mg n=268 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.	Aliskiren/Valsartan 300/320 mg n=278 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.
Percentage of Patients With a Cardiac Event	2.9 Percentage of patients	4.9 Percentage of patients	4.9 Percentage of patients	4.0 Percentage of patients

SECONDARY outcome

Timeframe: Baseline to Week 8

A composite clinical-biochemical event was defined as at least one of the following events: cardiovascular death confirmed by adjudication, recurrent MI confirmed by adjudication, hospitalization for CHF confirmed by adjudication, and/or NT-proBNP =\> 200 pg/mL.

Outcome measures

Outcome measures
Measure	Placebo n=278 Participants Placebo tablets and capsules	Aliskiren 300 mg n=268 Participants Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.	Valsartan 320 mg n=268 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.	Aliskiren/Valsartan 300/320 mg n=278 Participants Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.
Percentage of Patients With a Composite Clinical-biochemical Event	79.5 Percentage of patients	73.5 Percentage of patients	77.2 Percentage of patients	75.2 Percentage of patients

Adverse Events

Placebo

Serious events: 26 serious events

Other events: 64 other events

Deaths: 0 deaths

Aliskiren 300 mg

Serious events: 39 serious events

Other events: 61 other events

Deaths: 0 deaths

Valsartan 320 mg

Serious events: 33 serious events

Other events: 51 other events

Deaths: 0 deaths

Aliskiren/Valsartan 300/320 mg

Serious events: 46 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=278 participants at risk Placebo tablets and capsules	Aliskiren 300 mg n=264 participants at risk Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.	Valsartan 320 mg n=268 participants at risk Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.	Aliskiren/Valsartan 300/320 mg n=279 participants at risk Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.
Cardiac disorders Angina pectoris	4.7% 13/278 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	3.4% 9/264 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	5.2% 14/268 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	2.9% 8/279 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.
Metabolism and nutrition disorders Hyperkalaemia	6.1% 17/278 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	6.1% 16/264 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	4.9% 13/268 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	4.7% 13/279 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.
Nervous system disorders Dizziness	5.4% 15/278 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	8.7% 23/264 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	4.9% 13/268 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	6.8% 19/279 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.
Nervous system disorders Headache	6.5% 18/278 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	3.8% 10/264 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	2.6% 7/268 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	3.6% 10/279 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.
Vascular disorders Orthostatic hypotension	5.0% 14/278 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	6.1% 16/264 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	4.5% 12/268 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.	4.7% 13/279 Safety set: All patients that received at least 1 dose of study drug. Missing values were not imputed. In the aliskiren group, 4 patients were excluded because they never received study drug. One patient who never received study drug was included in the safety set because he had a date for the end of study treatment on the study completion page.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
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Restriction type: OTHER