Microvascular AnginaNCT00424801
Effects of Intensive Long-Term Vasodilation in Hypertensive Patients With Microvascular Angina Pectoris
A study testing Lercanidipine, Valsartan and Nicorandil in people with Microvascular Angina and Hypertension, run by University of Aarhus at 1 site in Denmark.
Trial summary
The purpose of this study is to determine if long-term vasodilatory treatment is more effective than the standard treatment in hypertensive patients with microvascular angina pectoris Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Microvascular Angina, Hypertension
- What is being tested?
- Lercanidipine, Valsartan and Nicorandil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- Jan 2007to Dec 2008
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- hypertension
- angina pectoris CCS class II-IV
- objective signs of ischemia on exercise-ECG or myocardial SPECT
- no significant stenosis on angiography (minimal lumen diameter >50% of relevant reference segment)
Who cannot join
- known allergy to any study medication
- abnormal lab tests of clinical significance
- valvular disease of haemodynamic significance
- known secondary hypertension
- atrial fibrillation or other significant arrythmias
- myocardial infarction < 30 days before inclusion
Show all 18Show fewer
- resting angina < one week before inclusion
- known endocrine disease, nephropathy or hepatic disease
- present malignant disease
- pregnancy
- fertile women not using safe contraceptives > 6 months before inclusion. Use of contraceptives must continue 1 month after completion or retraction from the study
- body mass index > 30
- significant chronic obstructive lung disease (FEV1 < 1.5 l)
- participant in another study including test medicine
- present treatment with dipyridamole
- present treatment with phosphodiesterase-5-inhibitors that the patient does not want to discontinue during the study period
- heart transplanted patients
- patients with magnetizable metallic implants
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intensive Non-Sympathetic Activating Vasodilatory Treatment in Hypertensive Patients With Microvascular Angina Pectoris
The purpose of this study is to determine if long-term vasodilatory treatment is more effective than the standard treatment in hypertensive patients with microvascular angina pectoris
Read the detailed description
Patients with hypertension frequently develop angina pectoris. This can be caused by either epicardial stenotic disease or, equally frequent, by increased resistance in small resistance vessels - microvascular dysfunction. This increased resistance is caused by a process called remodelling, where the existing material in the vessel wall is rearranged around a smaller lumen, whereas the sensitivity of the smooth muscle cells to agonist stimuli is unchanged. Under resting conditions the resistance is determined by both the tone in the smooth muscle cells in the vessel walls and the structure of the vessels themselves (RREST). Under hyperemic conditions the muscles relax and the resistance is determined only by vessel structure (RMIN).
A literature survey of the various studies on this subject has shown that structural changes relates to tone rather than blood pressure. This suggests that resistance vessel structure will be normalized only by an antihypertensive treatment which normalizes RREST i.e. rely on vasodilatation as a cause of the antihypertensive effect more than reduction of cardiac output.
The main hypothesis is, that it is possible to reverse the structural changes in the resistance vessels by vasodilatory treatment for eight months, thereby achieving lower coronary and peripheral minimal resistance (as determined by MRI and plethysmography, respectively), higher work capacity on exercise-ECG and less tendency to angina in these patients.
We will include 80 patients with essential hypertension, angina pectoris CCS class II-III and signs of ischemia on exercise-ECG or myocardial SPECT, but without significant stenosis in angiography. The patients are randomised, in a parallel, open-label design, to either vasodilatory (lercanidipine, valsartan, doxazosin and nicorandil) or standard treatment (metoprolol, diltiazem and isosorbide mononitrate). The aim of treatment in both arms is BP below 120/80 and the protocol allows further add-on therapy to reach this goal. The patients will be followed for eight months with a titration period of two months. MRI, plethysmography, exercise-ECG and echocardiography will be performed before and after the study period. The primary endpoint is minimal coronary resistance as determined by MRI; secondary endpoints are peripheral vascular resistance as determined by plethysmography, work capacity and ischemia threshold on exercise-ECG or myocardial SPECT.
- Conditions
- Microvascular Angina, Hypertension
- Being tested
- Lercanidipine, Valsartan, Nicorandil, Doxazosin, Moxonidin
- Medical subject headings
- Microvascular Angina, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LercanidipineDrug
Also called Zanidip
Individual titration, max. dose 20 mg OD for 8 months
ValsartanDrug
Also called Diovan
Individual titration, max. dose 160 mg OD for 8 months
NicorandilDrug
Also called Angicor
Individual titration, max. dose 20 mg BD for 8 months
DoxazosinDrug
Also called Doxazosin "Stada"
Individual titration, max. dose 4 mg OD for 8 months
MoxonidinDrug
Also called Moxonidin "Alpharma"
Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 0,2 mg OD for 8 months
PindololDrug
Also called Visken
Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 10 mg OD for 8 months
Amiloride, hydrochlorothiazideDrug
Also called Sparkal
Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 1 tbl. OD for 8 months
| Study group | Role | What they receive |
|---|---|---|
| Vasodilatory | Experimental | Patients in this arm will receive intensive vasodilatory treatment to lower blood pressure Receives: Drug: Lercanidipine; Drug: Valsartan; Drug: Nicorandil; Drug: Doxazosin; Drug: Moxonidin; Drug: Pindolol; Drug: Amiloride, hydrochlorothiazide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimal coronary resistance
Measured: 8 months
Secondary outcomes (3)
Peripheral vascular resistance
Measured: 8 months
Work capacity
Measured: 8 months
Ischemia threshold
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2007 (estimated)
- Study startJan 2007
- Primary completionDec 2008 (estimated)
- Study completionDec 2008 (estimated)
Why it stopped: Due to recent findings relating MRI contrast to nephrogenic systemic fibrosis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Microvascular AnginaStudies of the same condition, open and under way.
- More trials run by University of AarhusThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Cardiovascular Research Academy, Danish Heart Foundation, Novartis
- Investigators
- Michael N Præstholm, MD, Principal investigator, University of AarhusKent L Christensen, MD, DrMSc, Study director, Aarhus Hospital, medical-cardiologic dept. AWon Yong Kim, MD, DrMSc, Study director, Skejby Hospital, cardiologic dept. BHans Erik Bøtker, MD, DrMSc, Study director, Skejby Hospital, cardiologic dept. B
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00424801
- Sponsor's protocol ID
- Vasointense
- Status last verified
- May 2009
- First submitted
- 19 Jan 2007
- Last updated
- 6 May 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intensive Non-Sympathetic Activating Vasodilatory Treatment in Hypertensive Patients With Microvascular Angina Pectoris
- ClinicalTrials.gov ID
- NCT00424801
- Acronym / sponsor ID
- Vasointense
- Conditions
- Microvascular Angina, Hypertension
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to recent findings relating MRI contrast to nephrogenic systemic fibrosis
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Danish Cardiovascular Research Academy, Danish Heart Foundation, Novartis
- Study start
- Jan 2007
- Primary completion
- Dec 2008 (estimated)
- Study completion
- Dec 2008 (estimated)
- First posted
- 22 Jan 2007 (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.
The purpose of this study is to determine if long-term vasodilatory treatment is more effective than the standard treatment in hypertensive patients with microvascular angina pectoris
Detailed description
Patients with hypertension frequently develop angina pectoris. This can be caused by either epicardial stenotic disease or, equally frequent, by increased resistance in small resistance vessels - microvascular dysfunction. This increased resistance is caused by a process called remodelling, where the existing material in the vessel wall is rearranged around a smaller lumen, whereas the sensitivity of the smooth muscle cells to agonist stimuli is unchanged. Under resting conditions the resistance is determined by both the tone in the smooth muscle cells in the vessel walls and the structure of the vessels themselves (RREST). Under hyperemic conditions the muscles relax and the resistance is determined only by vessel structure (RMIN).
A literature survey of the various studies on this subject has shown that structural changes relates to tone rather than blood pressure. This suggests that resistance vessel structure will be normalized only by an antihypertensive treatment which normalizes RREST i.e. rely on vasodilatation as a cause of the antihypertensive effect more than reduction of cardiac output.
The main hypothesis is, that it is possible to reverse the structural changes in the resistance vessels by vasodilatory treatment for eight months, thereby achieving lower coronary and peripheral minimal resistance (as determined by MRI and plethysmography, respectively), higher work capacity on exercise-ECG and less tendency to angina in these patients.
We will include 80 patients with essential hypertension, angina pectoris CCS class II-III and signs of ischemia on exercise-ECG or myocardial SPECT, but without significant stenosis in angiography. The patients are randomised, in a parallel, open-label design, to either vasodilatory (lercanidipine, valsartan, doxazosin and nicorandil) or standard treatment (metoprolol, diltiazem and isosorbide mononitrate). The aim of treatment in both arms is BP below 120/80 and the protocol allows further add-on therapy to reach this goal. The patients will be followed for eight months with a titration period of two months. MRI, plethysmography, exercise-ECG and echocardiography will be performed before and after the study period. The primary endpoint is minimal coronary resistance as determined by MRI; secondary endpoints are peripheral vascular resistance as determined by plethysmography, work capacity and ischemia threshold on exercise-ECG or myocardial SPECT.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vasodilatory | Experimental | Drug: Lercanidipine, Drug: Valsartan, Drug: Nicorandil, Drug: Doxazosin, Drug: Moxonidin, Drug: Pindolol, Drug: Amiloride, hydrochlorothiazidePatients in this arm will receive intensive vasodilatory treatment to lower blood pressure |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- hypertension
- angina pectoris CCS class II-IV
- objective signs of ischemia on exercise-ECG or myocardial SPECT
- no significant stenosis on angiography (minimal lumen diameter >50% of relevant reference segment)
Key exclusion criteria (18 listed)
- known allergy to any study medication
- abnormal lab tests of clinical significance
- valvular disease of haemodynamic significance
- known secondary hypertension
- atrial fibrillation or other significant arrythmias
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 |
|---|---|---|
| LercanidipineAlso: ZanidipIndividual titration, max. dose 20 mg OD for 8 months | Drug | Vasodilatory |
| ValsartanAlso: DiovanIndividual titration, max. dose 160 mg OD for 8 months | Drug | Vasodilatory |
| NicorandilAlso: AngicorIndividual titration, max. dose 20 mg BD for 8 months | Drug | Vasodilatory |
| DoxazosinAlso: Doxazosin "Stada"Individual titration, max. dose 4 mg OD for 8 months | Drug | Vasodilatory |
| MoxonidinAlso: Moxonidin "Alpharma"Possible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 0,2 mg OD for 8 months | Drug | Vasodilatory |
| PindololAlso: ViskenPossible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 10 mg OD for 8 months | Drug | Vasodilatory |
| Amiloride, hydrochlorothiazideAlso: SparkalPossible add-on therapy in case target blood pressure can not be reached with a combination of the other drugs in the Vasodilatory arm. Individual titration, max. dose 1 tbl. OD for 8 months | Drug | Vasodilatory |
Primary outcome
Minimal coronary resistance
Time frame: 8 months
3 secondary outcomes
Peripheral vascular resistance
Time frame: 8 months
Work capacity
Time frame: 8 months
Ischemia threshold
Time frame: 8 months
Results and safety
The study was stopped early (reason given: Due to recent findings relating MRI contrast to nephrogenic systemic fibrosis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2009.
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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.
Michael N Præstholm, MD principal investigator
University of Aarhus
Kent L Christensen, MD, DrMSc study director
Aarhus Hospital, medical-cardiologic dept. A
Won Yong Kim, MD, DrMSc study director
Skejby Hospital, cardiologic dept. B
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lercanidipine, Valsartan and Nicorandil in people with Microvascular Angina and Hypertension, run by University of Aarhus at 1 site in Denmark.
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 18 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 6 May 2009. 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 Denmark. 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: Due to recent findings relating MRI contrast to nephrogenic systemic fibrosis). 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?
Minimal coronary resistance (time frame: 8 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 6 May 2009.