HypertensionPISANCT01425242
Study on Anti-inflammatory Effect of Anti-hypertensive Treatment in Patients With Small AAA's and Mild Hypertension
A study testing Aliskiren and Amlodipine in people with Hypertension and Abdominal Aortic Aneurysm, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hypertension, Abdominal Aortic Aneurysm
- What is being tested?
- Aliskiren and Amlodipine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2011to Dec 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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
- Participation in any clinical investigation within four (4) weeks prior to first dose or longer if required by local regulations, and for any other limitation of participation based on local regulations.
- Patients who have undergone prior radionuclide treatment or examinations or X-ray examinations with a cumulative radiation exposure, which added to the radiation exposure of the current study, would exceed local limits.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label PET-observer-blinded Pilot Study of the Effect of Aliskiren- Versus Amlodipine-based Antihypertensive Treatment in Patients With Small Abdominal Aortic Aneurysm and Mild to Moderate Hypertension on Aneurysmal FDG-uptake
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.
Read the detailed description
Standard therapy of small AAAs currently consists of "watchful waiting" strategy with aggressive blood pressure control "Watchful waiting" includes an Ultrasound (more recently CT or MRI scan) every 12 months (for AAAs between 3.5 - 4.4 cm) or every 6 months (for AAAs between 4.5 and 5.5 cm) to observe. A growth rate of >7 mm/ 6 months has been suggested as a threshold for proceeding to aneurysm repair irrespective of aneurysm size. Clearly, there is need for a more sensitive method to evaluate the progress of AAA growth.
Recent publications have shown that evaluation of AAAs using FDG-uptake with PET-scan may identify small AAAs that are more prone to grow and/or rupture, as these AAAs as compared to normal aorta's show increased inflammatory activity , which is considered the major pathophysiological pathway. Evaluation of FDG-uptake is also sensitive enough to observe the short-term effects of endovascular intervention of large AAAs, as unpublished data show a statistically significant reduction in aneurismal FDG-uptake only 6 weeks after endovascular repair of large AAAs. Therefore, the change in aneurismal FDG-uptake may also be a very promising and sensitive method to evaluate treatment effects of medical interventions within a relatively short period of time (3 months).
Just as pressure unloading may represent an anti-inflammatory mechanism in endovascular repair of more advanced aneurysms, so may milder pressure unloading in moderately hypertensive individuals with smaller aneurysms display similar anti-inflammatory effects. Such a mild form of pressure unloading may be attainable with adequate anti-hypertensive drug therapy. In this context, however, a possible additional benefit may be that some anti-hypertensive drug classes have been proposed to exert specific anti-inflammatory effects relevant to aneurysm inflammation.
Local activation of multiple components of the renin angiotensin system has been implicated in both the development of aneurysms, as well as in their inflammatory component. In accordance, preliminary evidence from murine studies suggest that ACE inhibitors, for example, may reduce inflammatory activity in aneurysmatic vessel walls. However, since ACE inhibitors block the renin angiotensin system halfway it's path, and non-ACE conversion of angiotensin I occurs, a rationale exists to block the renin angiotensin system upstream of ACE. Upstream blockade of the renin-angiotensin system may have additional advantages in antagonising direct pro-inflammatory effects of renin itself, which have been identified in, for example, kidney tissue and retinal microvessels.
A case can thus be made for renin inhibition as a potential optimal strategy for reducing aneurysm inflammation in hypertensive patients with aortic aneurysms. In the proposed pilot trial, the direct renin inhibitor Aliskiren will be evaluated. As a control condition, an antihypertensive agent without postulated specific anti-inflammatory effects is appropriate. Calcium channel blockers represent such a class.
The current study will explore what the size and variability of the effect of aliskiren monotherapy, the combination of aliskiren/hydrochlorothiazide, amlodipine monotherapy, or the combination of amlodipine/hydrochlorothiazide on FDG-uptake is (if at all measurable on top of the effect of antihypertensive and statin therapy). This will allow more accurate power calculation of larger future studies aiming at prevention of AAA-progression (diameter and rupture).
- Conditions
- Hypertension, Abdominal Aortic Aneurysm
- Being tested
- Aliskiren, Amlodipine
- Keywords
- inflammation, aneurysm, hypertension, aliskiren
- Medical subject headings
- Hypertension, Aortic Aneurysm, Abdominal, Inflammation, Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AliskirenDrug
Also called Rasilez
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.
AmlodipineDrug
Also called Norvasc
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Amlodipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in aneurysmal vessel wall inflammation
Change from baseline in aneurismal FDG-uptake as measured with PET-CT after 3 and 12 months
Measured: 3 months and 12 months
Secondary outcomes (2)
Change in abdominal aortic aneurysm diameter
Change from baseline in aneurismal diameter after 12 months
Measured: 12 months
Change in large vessel inflammation
Change from baseline in FDG-uptake in other large blood vessels after 3 and 12 months
Measured: 3 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2011 (estimated)
- Study startSep 2011
- Primary completionDec 2013
- Study completionDec 2013
Why it stopped: Insufficient number of participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, Jan D. Blankensteijn, Amsterdam UMC, location VUmc
- Investigators
- Jan D Blankensteijn, MD, PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01425242
- Sponsor's protocol ID
- AAA-PET/CT vumc
- Other IDs
- 2011-000538-12
- Acronym
- PISA
- Status last verified
- Dec 2014
- First submitted
- 26 Aug 2011
- Last updated
- 9 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label PET-observer-blinded Pilot Study of the Effect of Aliskiren- Versus Amlodipine-based Antihypertensive Treatment in Patients With Small Abdominal Aortic Aneurysm and Mild to Moderate Hypertension on Aneurysmal FDG-uptake
- ClinicalTrials.gov ID
- NCT01425242
- Acronym / sponsor ID
- PISA / AAA-PET/CT vumc
- Conditions
- Hypertension, Abdominal Aortic Aneurysm
- Keywords
- inflammation, aneurysm, hypertension, aliskiren
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient number of participants
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Sep 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 29 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Standard therapy of small AAAs currently consists of "watchful waiting" strategy with aggressive blood pressure control "Watchful waiting" includes an Ultrasound (more recently CT or MRI scan) every 12 months (for AAAs between 3.5 - 4.4 cm) or every 6 months (for AAAs between 4.5 and 5.5 cm) to observe. A growth rate of >7 mm/ 6 months has been suggested as a threshold for proceeding to aneurysm repair irrespective of aneurysm size. Clearly, there is need for a more sensitive method to evaluate the progress of AAA growth.
Recent publications have shown that evaluation of AAAs using FDG-uptake with PET-scan may identify small AAAs that are more prone to grow and/or rupture, as these AAAs as compared to normal aorta's show increased inflammatory activity , which is considered the major pathophysiological pathway. Evaluation of FDG-uptake is also sensitive enough to observe the short-term effects of endovascular intervention of large AAAs, as unpublished data show a statistically significant reduction in aneurismal FDG-uptake only 6 weeks after endovascular repair of large AAAs. Therefore, the change in aneurismal FDG-uptake may also be a very promising and sensitive method to evaluate treatment effects of medical interventions within a relatively short period of time (3 months).
Just as pressure unloading may represent an anti-inflammatory mechanism in endovascular repair of more advanced aneurysms, so may milder pressure unloading in moderately hypertensive individuals with smaller aneurysms display similar anti-inflammatory effects. Such a mild form of pressure unloading may be attainable with adequate anti-hypertensive drug therapy. In this context, however, a possible additional benefit may be that some anti-hypertensive drug classes have been proposed to exert specific anti-inflammatory effects relevant to aneurysm inflammation.
Local activation of multiple components of the renin angiotensin system has been implicated in both the development of aneurysms, as well as in their inflammatory component. In accordance, preliminary evidence from murine studies suggest that ACE inhibitors, for example, may reduce inflammatory activity in aneurysmatic vessel walls. However, since ACE inhibitors block the renin angiotensin system halfway it's path, and non-ACE conversion of angiotensin I occurs, a rationale exists to block the renin angiotensin system upstream of ACE. Upstream blockade of the renin-angiotensin system may have additional advantages in antagonising direct pro-inflammatory effects of renin itself, which have been identified in, for example, kidney tissue and retinal microvessels.
A case can thus be made for renin inhibition as a potential optimal strategy for reducing aneurysm inflammation in hypertensive patients with aortic aneurysms. In the proposed pilot trial, the direct renin inhibitor Aliskiren will be evaluated. As a control condition, an antihypertensive agent without postulated specific anti-inflammatory effects is appropriate. Calcium channel blockers represent such a class.
The current study will explore what the size and variability of the effect of aliskiren monotherapy, the combination of aliskiren/hydrochlorothiazide, amlodipine monotherapy, or the combination of amlodipine/hydrochlorothiazide on FDG-uptake is (if at all measurable on top of the effect of antihypertensive and statin therapy). This will allow more accurate power calculation of larger future studies aiming at prevention of AAA-progression (diameter and rupture).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aliskiren | Experimental | Drug: AliskirenHalf 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 |
| Amlodipine | Active comparator | Drug: AmlodipineHalf 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AliskirenAlso: RasilezStarting 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. | Drug | Aliskiren |
| AmlodipineAlso: NorvascStarting 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. | Drug | Amlodipine |
Primary outcome
Change in aneurysmal vessel wall inflammation
Time frame: 3 months and 12 months
Change from baseline in aneurismal FDG-uptake as measured with PET-CT after 3 and 12 months
2 secondary outcomes
Change in abdominal aortic aneurysm diameter
Time frame: 12 months
Change in large vessel inflammation
Time frame: 3 months and 12 months
Results and safety
The study was stopped early (reason given: Insufficient number of participants). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan D Blankensteijn, MD, PhD principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aliskiren and Amlodipine in people with Hypertension and Abdominal Aortic Aneurysm, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Insufficient number of participants). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in aneurysmal vessel wall inflammation (time frame: 3 months and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2014.