Efficacy of Aliskiren Compared to Ramipril in the Treatme... | NCT01042392

ID	Type	Description	Link
2009-011296-80	EudraCT Number

Status Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ramipril	Active Comparator	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).	Drug: Ramipril Drug: Matching placebo to Aliskiren
Aliskiren	Experimental	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal ): At visit 4, part of the patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).	Drug: Aliskiren Drug: Matching placebo to Ramipril
Placebo to Ramipril	Placebo Comparator	In period III (double-blind withdrawal ): At visit 4, part of patients from Ramipril arm received placebo to Ramipril for 1 day. The study ended at visit 5 (48 hours later than visit 4).	Drug: Matching placebo to Ramipril
Placebo to Aliskiren	Placebo Comparator

Name	Type	Description	Arm Group Labels	Other Names
Aliskiren	Drug	150 mg Aliskiren as film-coated tablet	Aliskiren
Ramipril

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of covariance included treatment factor and baseline mean sitting SBP as covariable.	Baseline to 8 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of variance included treatment factor and baseline value of mean sitting DBP as covariable.

Eligibility Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Aire Sur Adour			France
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33089502	Derived	Wang GM, Li LJ, Tang WL, Wright JM. Renin inhibitors versus angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database Syst Rev. 2020 Oct 22;10(10):CD012569. doi: 10.1002/14651858.CD012569.pub2.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
BG001	Aliskiren	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00059.8± 11.6 BG00161.0± 11.4 BG00260.4± 11.5

Age, Customized

Number

Participants

Title

Denominators

Categories

< 50 years

Title	Measurements
	BG00056 BG00139 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000142 BG001133 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)

The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of covariance included treatment factor and baseline mean sitting SBP as covariable.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline to 8 weeks

ID	Title	Description
OG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
OG001	Aliskiren	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).

Units	Counts
Participants	OG000213 OG001213

Title

Denominators

Categories

Title	Measurements
	OG000-18.80± 0.92 OG001-20.78± 0.92

Secondary

Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)

The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of variance included treatment factor and baseline value of mean sitting DBP as covariable.

Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with observation at both time points were included in this analysis.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline to 8 weeks

ID	Title	Description
OG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
OG001	Aliskiren

Secondary

Percentage of Patients With Controlled Blood Pressure

Controlled blood pressure (BP) is defined as mean office systolic BP/ diastolic BP < 140/90 mmHg.

Posted

Number

Percentage

At 4 and 8 weeks

ID	Title	Description
OG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
OG001	Aliskiren

Secondary

Number of the Participants With More Than 55 mmHg Difference Between the Mean SBP Measured at the Morning Surge and the Mean Minimal SBP Measured During the Night

Ambulatory blood pressure measurement (ABPM) over 24 hours was performed for all patients on the day before visit 4, the device attached to the ambulatory blood pressure non-dominant arm of the patient. The BP morning surge was defined as the average of the measurements taken during the first 2 hours after waking the patient. The minimal night blood pressure was defined as the average of the two lowest BP measures (the lowest hourly average) recorded during night time.

Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with ABPM to evaluate the occurrence or absence of a morning peak were included in this analysis.

Posted

Number

Participants

After 8 weeks

ID	Title	Description
OG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
OG001

Secondary

Change in msSBP and msDBP From Visit 2 (Baseline) to Visit 3 (at 4 Weeks)

Posted

Least Squares Mean

Standard Error

mmHg

Baseline to 4 weeks

ID	Title	Description
OG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
OG001	Aliskiren

Secondary

Difference Between the Maximal and the Minimal Mean-hour SPB Measured Between 1 and 8 am at Week 8

Ambulatory blood pressure measurement (ABPM) over 24 hours was performed for all patients on the eve of visit 4 (week 8), the device attached to the ambulatory blood pressure non-dominant arm of the patient. The difference between mean-hour maximum SBP mean-hour minimum SBP between 1 am and 8 am was measured.

Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with ABPM measurements over 24 hours were included in this analysis.

Posted

Mean

Standard Deviation

mmHg

At week 8

ID	Title	Description
OG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
OG001	Aliskiren	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).

Secondary

Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks)

The sub-groups were: "Riser" = patients with >= 55 mmHg difference between the mean SPB measured at the morning surge and the mean minimal SBP measured during the night. The "Non-risers" in whom the difference is <55 mmHg. Patients called "dippers" in whom there was a decrease in average nocturnal SBP ≥ 10% compared with average daytime SBP, in contrast to patients "non-dippers " in whom this difference was <10%.

Posted

Mean

Standard Deviation

mmHg

Baseline to 8 weeks

ID	Title	Description
OG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
OG001	Aliskiren

Secondary

Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) From Last Active Dose Taken to After a One-day Missed-dose

The change in blood pressure was measured between visit 4 (end of the period of double-blind active treatment which was at week 8) and visit 5 (48 hours after the last active dose taken) in the group of patients who received aliskiren or placebo and those who received ramipril or placebo. The analysis of covariance included treatment factor and baseline mean sitting SBP and mean sitting DBP as covariables.

Per-protocol missed dose population included all per protocol population patients who had received the study treatment for period 3 according to the protocol (duration of period 3 and treatment intake). Patients with observation at both time points were included in this analysis.

Posted

Least Squares Mean

Standard Error

mmHg

From 8 weeks to 48 hours after week 8

ID	Title	Description
OG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
OG001	Placebo to Ramipril

Secondary

Number Patients Reported With Adverse Events (AEs), Serious Adverse Events (SAE) and Death (Period II and Period III)

Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

All randomized patients except one patient from Aliskiren arm who was lost to follow up after visit 2.

Posted

Number

Participants

8 weeks + 1 day

ID	Title	Description
OG000	Ramipril	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
OG001	Aliskiren

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (At Risk)
EG000	Ramipril (Period II and III)	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).	3	257	257
EG001	Placebo to Ramipril (Period III)	In period III (double-blind withdrawal): At visit 4, part of the patients from Ramipril arm received placebo to Ramipril for 1 day. The study ended at visit 5 (48 hours later than visit 4).	0	118	118
EG002	Aliskiren (Period II and III)	In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).	1	248	248
EG003	Placebo to Aliskiren (Period III)	In period III (double-blind withdrawal): At visit 4, part of patients from Aliskiren arm received placebo for 1 day. The study ended at visit 5 (48 hours later than visit 4).	0	122	122

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
normochromic normocytic anemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected257 at risk EG0010 affected118 at risk EG0021 affected248 at risk EG0030 affected122 at risk
spine metastasis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected257 at risk EG0010 affected118 at risk EG0021 affected248 at risk EG003
cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected257 at risk EG0010 affected118 at risk EG0021 affected248 at risk EG003
bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected257 at risk EG0010 affected118 at risk EG0021 affected248 at risk EG003
liver metastatis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected257 at risk EG0010 affected118 at risk EG0021 affected248 at risk EG003
abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected257 at risk EG0010 affected118 at risk EG0020 affected248 at risk EG003
pancreatic adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected257 at risk EG0010 affected118 at risk EG0020 affected248 at risk EG003
dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected257 at risk EG0010 affected118 at risk EG0020 affected248 at risk EG003
atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected257 at risk EG0010 affected118 at risk EG0020 affected248 at risk EG003
asthenia	General disorders	MedDRA	Systematic Assessment	EG0001 affected257 at risk EG0010 affected118 at risk EG0020 affected248 at risk EG003

In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.

In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4.

In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).

In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.

In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).

In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.

In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).

In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in.

In period III (double-blind withdrawal): At visit 4, patients received placebo or the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).

ID	Term
D006973	Hypertension
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Term
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds