A randomized, 32 week double-blind, parallel-group, multicenter study to compare the efficacy and safety of initiating treatment with combination (aliskiren/amlodipine) therapy in comparison with the sequential add-on treatment strategies in patients with essential hypertension. - ACCELERATE: Aliskiren and the Calcium Channel BlockEr amLodipine combination as an initial trEatment

• Register: EUCTR
• Last refreshed on: 26 January 2015
• Main ID: EUCTR2008-004242-83-FR
• Date of registration: 21/10/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, 32 week double-blind, parallel-group, multicenter study to compare the efficacy and safety of initiating treatment with combination (aliskiren/amlodipine) therapy in comparison with the sequential add-on treatment strategies in patients with essential hypertension. - ACCELERATE: Aliskiren and the Calcium Channel BlockEr amLodipine combination as an initial trEatment
• Scientific title: A randomized, 32 week double-blind, parallel-group, multicenter study to compare the efficacy and safety of initiating treatment with combination (aliskiren/amlodipine) therapy in comparison with the sequential add-on treatment strategies in patients with essential hypertension. - ACCELERATE: Aliskiren and the Calcium Channel BlockEr amLodipine combination as an initial trEatment
• Date of first enrolment: 28/11/2008
• Target sample size: 1236
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004242-83
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: aliskiren and amlodipine in sequential add-on treatment

Countries of recruitment

France, Germany, Greece, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female outpatients = 18 years of age
2. Patients with essential hypertension:
• Naïve patients must have a msSBP = 150 mmHg and < 180 mmHg at Visit 1 and Visit 2. (Patients are considered ‘naïve’ if they have never been treated with any antihypertensive medication.)
• All patients must have a msSBP = 150 mmHg and < 180 mmHg at Visit 2
3. Written informed consent to participate in this study prior to any study procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
For full list, please refer to the protocol, pages 8 to 10.

1. Patients previously treated in an aliskiren study that contained the treatment group of the combination of aliskiren and amlodipine and had been randomized or enrolled into the active drug treatment period of that study.
2. Severe hypertension (msDBP = 110 mmHg and/or msSBP = 180 mmHg).
3. Pregnant or nursing (lactating) women, where pregnancy is defined as a state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (= 5 mIU/ml).
4. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method (if accepted by local ethics committee) or a barrier method plus a hormonal method.
• Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent.
Reliable contraception should be maintained throughout the study and for 7 days after the study.
• Woman are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml [for US only: and estradiol < 20 pg/ml] or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
5. History or evidence of a secondary form of hypertension.
6. Known Keith-Wagener grade III or IV hypertensive retinopathy.
7. Any history of hypertensive encephalopathy or cerebrovascular accident, or history within 12 months from visit 1 for transient ischemic attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI).
8. Previous or current diagnosis of heart failure (NYHA Class II-IV).
9. Serum potassium = 5.5 mEq/L (mmol/L) at Visit 1.
10. Patients with Type 1 or Type 2 diabetes mellitus who are not well controlled based on the investigator's clinical judgment. Patients with diabetes mellitus enrolled in this study should be well controlled. It is recommended that patients currently being treated for diabetes mellitus be on a stable dose of antidiabetic medication for at least 4 weeks prior Visit 1.
11. Current angina pectoris requiring pharmacological therapy except for nitrates.
12. Second or third degree heart block without a pacemaker.
13. Atrial fibrillation or atrial flutter at Visit 1, or potentially life threatening arrhythmia during the 12 months prior to Visit 1.
14. Clinically symptomatic valvular heart disease at Visit 1.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

essential hypertension
MedDRA version: 9.1 Level: LLT Classification code 10015488 Term: Essential hypertension

Intervention(s)

Trade Name: Rasilez
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: aliskiren
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Rasilez
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: aliskiren
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Norvasc
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: amlodipine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Norvasc
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: amlodipine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: hydrochlorothiazide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 1. To evaluate if initiating treatment with a combination is superior compared to the average of the sequential add-on treatment strategies in reduction of the overall mean over weeks 8, 16, and 24 in the change from baseline in msSBP
2. To evaluate under proof of principle that starting treatment with a combination regimen is superior compared to the average of the sequential add-on treatment strategies in final achieved reduction from baseline to week 24 in msSBP

Primary end point(s): The primary efficacy variable for the first rank order hypothesis will be the overall mean of the changes from baseline in msSBP over the three time points: Weeks 8, 16 and 24. The primary efficacy variable for the second rank order hypothesis will be the change from baseline in msSBP at Week 24 (Visit 5).

Secondary Objective: Key secondary objectives are listed below. For full list, please refer to the protocol.

• To compare the average change from baseline in msSBP over weeks 8, 16, and 24 between the starting combination group and the sequential add-on treatment groups
• To compare the average change from baseline in mean sitting diastolic blood pressure (msDBP) over weeks 8, 16, and 24 between the starting combination group and the sequential add-on treatment groups (single and combined)
• To compare the change from baseline in msSBP and msDBP after 8, 16, and 32 weeks between the starting combination group and the sequential add-on treatment groups (single and combined)
• To evaluate the safety and tolerability in all treatment groups

Secondary ID(s)

2008-004242-83-DE

CSPA100A2307