Study on Anti-inflammatory Effect of Anti-hypertensive Treatment in Patients With Small AAA's and Mild Hypertension

NCT01425242 | Terminated

• 2 other identifiers: AAA-PET/CT vumc2011-000538-12
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Inflammation of the blood vessel plays an important role in the development and growth of a dilated abdominal aorta. An elevated blood pressure leads to an increase in inflammation, therefore blood pressure lowering is an important part of the treatment of patients with a dilated abdominal aorta who also have an elevated blood pressure. In the investigators study the investigators compare the anti-inflammatory effects of 2 different blood pressure lowering strategies. The investigators hypothesize that both strategies will decrease inflammation, however the investigators believe the total decrease of inflammation depends on the type of blood pressure lowering medication used.

Conditions

Hypertension; Abdominal Aortic Aneurysm

Keywords

inflammation; aneurysm; hypertension; aliskiren

Outcome Measures

Primary Outcomes (1)

• Change in aneurysmal vessel wall inflammation

  Change from baseline in aneurismal FDG-uptake as measured with PET-CT after 3 and 12 months

  3 months and 12 months

Secondary Outcomes (2)

• Change in abdominal aortic aneurysm diameter

  12 months

• Change in large vessel inflammation

  3 months and 12 months

Study Arms (2)

Aliskiren

EXPERIMENTAL

Half of all subjects with mild to moderate hypertension and a small abdominal aortic aneurysm are treated with aliskiren, combined with hydrochlorothiazide if hypertension cannot be treated sufficiently with aliskiren monotherapy

Drug: Aliskiren

Amlodipine

ACTIVE COMPARATOR

Half of all subjects with mild to moderate hypertension and a small abdominal aortic aneurysm are treated with amlodipine, combined with hydrochlorothiazide if hypertension cannot be treated sufficiently with amlodipine monotherapy

Drug: Amlodipine

Interventions

Aliskiren DRUG

Starting dose: Aliskiren 150 mg p.o, if hypertension is insufficiently treated Hydrochlorothiazide 12.5 mg p.o. tablet once daily for maximally 12 months can be added, the next step is to add increase the dosage of Aliskiren to 300 mg p.o. tablet once daily until maximally 12 months after baseline, the final step to take in case hypertension is still present is to increase Hydrochlorothiazide to 25 mg p.o. tablet once daily until maximally 12 months after baseline.

Also known as: Rasilez

Aliskiren

Amlodipine DRUG

Starting dose: amlodipine 5 mg p.o, if hypertension is insufficiently treated Hydrochlorothiazide 12.5 mg p.o. tablet once daily for maximally 12 months can be added, the next step is to add increase the dosage of amlodipine to 10 mg p.o. tablet once daily until maximally 12 months after baseline, the final step to take in case hypertension is still present is to increase Hydrochlorothiazide to 25 mg p.o. tablet once daily until maximally 12 months after baseline.

Also known as: Norvasc

Amlodipine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a proven AAA of \>30 mm and \< 55 mm
• Age between 18 and 75y (both inclusive)
• Weight \> 50 kg
• Mild to moderate hypertension (defined as 130 \< msSBP \< 180 or 85\< msDBP \<110), at screening and/or baseline, without current antihypertensive medication.

You may not qualify if:

• Patients without an AAA, or with an AAA ≥ 55 mm, or ≤ 30 mm
• Patients with an AAA who are eligible for surgical repair for any reason
• Diabetes mellitus
• Inability of the subjects to switch from all prior antihypertensive medications safely as required by the protocol and need for drugs other than study drugs at the time of baseline
• Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg) at screening and/or baseline
• Pregnant or nursing (lactating) women
• Known or suspected contraindications, including history of allergy or hypersensitivity (such as angioedema) to DRIs, CCBs, ACEIs, statins, acetylsalicylic acid or diuretics in general (for example, to aliskiren / amlodipine / hydrochlorothiazide / statins)
• Concomitant drugs that are strong inhibitors of CYP3A4 or P-glycoprotein inhibitors (ketoconazole, itraconazole, nefazodone, clarithromycin, ritonavir, nelfinavir, cyclosporine, verapamil, quinidine)
• Previous or current diagnosis of heart failure (NYHA Class II-IV)
• Second or third degree heart block without a pacemaker, or potentially life-threatening arrhythmia during the 12 months prior to screening
• Clinically symptomatic valvular heart disease at screening visit
• A past medical history of clinically significant ECG abnormalities
• Confirmed serum potassium ≥5.3 mEq/L (mmol/L) at screening or baseline.
• Impaired renal function, defined as eGFR \< 45 mL/min/1.73 m2 MDRD
• Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Novartis: collaborator

Study Sites (1)

VU University Medical Center

Amsterdam, 1007 MB, Netherlands

Location

MeSH Terms

Conditions

Hypertension; Aortic Aneurysm, Abdominal; Inflammation; Aneurysm

Interventions

aliskiren; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Aortic Aneurysm; Aortic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jan D Blankensteijn, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: August 26, 2011
• First Posted: August 29, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 9, 2014

Record last verified: 2014-12

Locations

NL (1)