Clinical trial NCT00927394: Aliskiren and Valsartan vs Valsartan Alone in Patients With Stage II Systolic Hypertension and Type II Diabetes Mellitus
Official title: An 8 Week Randomized, Double-Blind, Parallel Group, Multi-Center, Active Controlled Study to Evaluate the Antihypertensive Efficacy and Safety of Aliskiren Administered in Combination With Valsartan Versus Valsartan Alone in Patients With Stage 2 Systolic Hypertension and Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: Hypertension, Type II Diabetes, Aliskiren, Valsartan,
Systolic blood pressure, Diastolic blood pressure,
Stage II, Combination
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-06-25
Enrollment: 1143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study was to evaluate the blood pressure (BP)-lowering efficacy of the combination of aliskiren and valsartan, as initial therapy, compared to valsartan monotherapy in Type II Diabetic patients with Stage II hypertension.

Detailed description: When protocol Amendment 2 was released, there were patients who had already been randomized into the study. These patients were included in the trial prior to making changes to the eligibility criteria. Thus, the study contains 2 distinct cohorts. Cohort 1 contains those patients who had already been randomized, and had been deemed eligible based on the original inclusion/exclusion criteria, prior to Amendment 2. No new patients were randomized to Cohort 1. Cohort 2 contains patients who were randomized, having been found eligible based on the revised inclusion/exclusion criteria, after Amendment 2. Differences in the inclusion and exclusion criteria are indicated below.

Eligibility criteria: Inclusion Criteria:

* Patients who are eligible and able to participate in the study, and who give written informed consent before any assessment is performed.
* Men or women 18 years and older.
* Patients with Type 2 diabetes mellitus with an HbA1c ≤ 9 % at visit 1 and on a stable anti-diabetic regimen not including insulin or stable diet and exercise for at least 4 weeks prior to visit 1.

Cohort 1:

* Patients with Stage 2 systolic hypertension, defined as having a MSSBP ≥160 mmHg and \<200 mmHg at Visit 5 (randomization).
* Patients who have been newly diagnosed with hypertension or who have not received antihypertensive medication for at least 4 weeks (28 days) prior to Visit 1 must have MSSBP ≥ 160 mmHg and \< 200 mmHg at Visit 1, otherwise, they will be considered screen failures.
* Patients receiving antihypertensive medication must have a MSSBP of ≥150 mmHg and \<200 mmHg at Study Visit 1, otherwise they will be considered screen failures.

Cohort 2:

* Patients must also have had a mean 8-hour daytime ambulatory systolic blood pressure (ASBP) ≥140 mmHg AND mean 8-hour daytime ambulatory diastolic blood pressure (ADBP) ≥90 mmHg at Visit 5 (randomization).
* Hypertensive patients with MSSBP ≥150 mmHg and but \<200 mmHg AND MSDBP ≥95 but \<120 mmHg at Visit 5 (randomization).
* Patients who had been newly diagnosed with hypertension or who had not received antihypertensive medication for at least 4 weeks (28 days) prior to Visit 1 must have had MSSBP ≥150 mmHg but \<200 mmHg and MSDBP ≥95 but \<120 mmHg at Visit 1, otherwise, they were considered screen failures.

Exclusion Criteria:

* Office blood pressure measured by cuff (MSSBP ≥200 mmHg or MSDBP ≥120 mmHg).
* History or evidence of secondary hypertension of any etiology.
* Refractory hypertension, defined as having uncontrolled BP (≥140/90 mmHg) while receiving 3 antihypertensive medications at the maximum approved dose of each drug, one of which must be a diuretic.
* Patients treated with more than 3 antihypertensive medications (each component of a combination drug counts individually).
* Type 2 diabetes mellitus currently requiring insulin treatment.
* modification of diet in renal disease (MDRD) estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2
* Serum sodium less than lower limit of normal, serum potassium \< 3.5 mEq/L or ≥ 5.3 mEq/L at Visit 1.
* Known Keith-Wagener grade III or IV hypertensive retinopathy.

Cohort 1:

- Patients with known diabetic retinopathy (eg, having a history of laser therapy for diabetic retinopathy) or diabetic neuropathy (eg, receiving medication for diabetic neuropathy).

Cohort 2:

- Patients with known diabetic retinopathy or diabetic neuropathy and/or having a history of treatment for either.

Other protocol-defined inclusion/exclusion criteria applied.

Primary outcomes:
measure: Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure (MASBP) at Week 8
timeFrame: baseline, week 8
Secondary outcomes:
measure: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP)
timeFrame: Baseline, week 8
measure: Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (MADBP) at Week 8
timeFrame: baseline, week 8
measure: Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (MAPP) at Week 8
timeFrame: baseline, week 8
measure: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)
timeFrame: Baseline, week 8
measure: Change From Baseline in Mean Sitting Pulse Pressure (MSPP) at Week 8
timeFrame: baseline, week 8
measure: Percentage of Patients Achieving Blood Pressure Control
timeFrame: 8 weeks
measure: Percentage of Responders
timeFrame: Baseline, Week 8
measure: Change From Baseline in Plasma Renin Activity (PRA) at Week 8
timeFrame: Baseline, week 8
measure: Change From Baseline in Plasma Renin Concentration (PRC) at Week 8
timeFrame: Baseline, week 8
measure: Change From Baseline in Plasma Aldosterone at Week 8
timeFrame: Baseline, week 8
measure: Number of Patients With Adverse Events, Serious Adverse Events and Death
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Newark
country: United States
facility: Investigative Site
state: Delaware
city: Kansas
country: United States
facility: Investigative Site
state: Missouri
city: Camden
country: United States
facility: Investigative Site
state: New Jersey
city: Philadelphia
country: United States
facility: Investigative Site
state: Pennsylvania
Study officials:
affiliation: Novartis
name: Novartis
role: STUDY_DIRECTOR
References:
citation: Bakris GL, Oparil S, Purkayastha D, Yadao AM, Alessi T, Sowers JR. Randomized study of antihypertensive efficacy and safety of combination aliskiren/valsartan vs valsartan monotherapy in hypertensive participants with type 2 diabetes mellitus. J Clin Hypertens (Greenwich). 2013 Feb;15(2):92-100. doi: 10.1111/jch.12032. Epub 2012 Oct 26.