The primary aim of the trial is to assess what the optimal treatment regimen for acetylsalicylic acid, a statin and two BP-lowering agents is (administered as in regular care in individual agents, a fixed-dose combination pill administered in the…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Central nervous system vascular disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Difference in LDL cholesterol between treatment regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
• Difference in mean 24 hour ambulatory systolic BP between treatment regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
Secondary outcome
• Difference in lipid fractions between treatment regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
• Difference in platelet function between treatment regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
• Difference in 24 hour ambulatory BP parameters between treatment regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
• Difference in central blood pressure between treatment regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
• Difference in cardiovascular risk score (Framingham) between treatment
regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
• Difference in adherence (electronic event monitoring) between treatment
regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
• Difference in adverse events between treatment regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
• Difference in participant acceptability between treatment regimen
(evening administration RHP vs morning administration RHP vs administration of
individual agents)
Background summary
It is expected that a single pill administered on fixed time will simplify
medication intake for patient compared to several separate agents on various
times, thereby controlling the cardiovascular risk better. However, the
components of the polypill need to be administered on various time points. In
clinical practice, anti-hypertensives are generally prescribed for use in the
morning, whereas some statins are recommended for use in the evening. There is
evidence that the reduction in LDL achieved with some statins is superior when
taken in the night, but it is unclear whether the additional reduction in LDL
(and the reported improvement in BP control when aspirin is taken in the
evening) is offset by a reduction in adherence when taking medication in the
evening. The current goal is to assess what the optimal treatment regimen is
for cardiovascular medication in terms of the change in mean LDL cholesterol
levels and ambulatory systolic BP, and adherence to therapy.
Study objective
The primary aim of the trial is to assess what the optimal treatment regimen
for acetylsalicylic acid, a statin and two BP-lowering agents is (administered
as in regular care in individual agents, a fixed-dose combination pill
administered in the evening or administered in the morning), in terms of the
change in mean ambulatory systolic BP and/or LDL cholesterol levels in
individuals at intermediate or high risk of cardiovascular disease.
Study design
Randomized cross-over study with 75 participants.
Intervention
Eligible individuals willing to participate in the trial will receive the
polypill and the components of the polypill for a total of 18-24 weeks; a
random sequence of 6 weeks morning, 6 weeks evening administration and 6 weeks
administration of the individual agents. After every treatment sequence
laboratory blood examination and ambulatory blood measurements will be
performed.
Study burden and risks
Measurements:
None of the study measurements are dangerous. Routine blood samples taken may
be associated with somen bruising, discomfort and local irritation. There is
also a smal risk of infection whenever the skinbarrier is broken by a needle.
The ABPM may be incomfortable due to 24 hours measurement every 30 minutes,
including at night. This last measurement may be inconvenient.
Medication:
The polypill combination cardiovascular medication will be an unapproved
medication. However all the ingredients in both of the polypill combinations
used in this trial are well knowm midicines with well established efficacy and
safety profiles. Although all the drugs in the polypill haven been used for
many years there are possible risks that both polypill may cause side effects.
These are generally mild and infrequent and are usally resolved immediatly by
stopping the medication. Side effects of the components of the polypills can
include low bloodpressure, dizziness, headache, nausea, mild stomach pain,
heartburn, ulceration, abdominal pain, constipation, flatulance, bleeding,
gout, cough, fatique, liver problems, ans muscle pain, tenderness or weakness.
As with any medication an allergic reaction is possible such as skin rash,
itching, difficulty breathing or swelling of the face, but this is quite rare.
Heidelberglaan 100
Utrecht 3508 GA
NL
Heidelberglaan 100
Utrecht 3508 GA
NL
Listed location countries
Age
Inclusion criteria
Adults (>= 18 years) with:
- (A) established atherothrombotic cardiovascular disease (CVD)- history of ischaemic heart disease, ischaemic stroke or transient ischaemic attack, or peripheral vascular disease.
OR
- (B) a 5 year cardiocvascular risk of at least 10% (Framingham risk equation, New Zealand Guidelines Group approach).;- The trial investigator and the specialist from the department of Vascular Medicine considers that the polypill components are indicated according to current guidelines at the doses in the Red Heart Pill 2c.
Exclusion criteria
Individuals will NOT be eligible if one or more of the following criteria are satisfied:
• Contraindication to any of the components of the polypill (e.g. known intolerance to aspirin, statins, or ACE inhibitors; pregnancy or likely to become pregnant or breastfeeding women during the treatment period). Such contrindications are fully listed in the Investigator Brochure.
• The treating doctor or trial doctor considers that changing a participant*s cardiovascular medications would put the participant at risk (e.g. symptomatic heart failure, high dose β-blocker required to manage angina or for rate control in atrial fibrillation, accelerated hypertension, severe renal insufficiency, a history of severe resistant hypertension).;Other potential reasons for exclusion include:
• Known situation where medication regimen might be altered for a significant length of time, e.g. current acute cardiovascular event(s), planned coronary bypass graft operation.
• Unlikely to complete the trial (e.g. life-threatening condition other than cardiovascular disease) or adhere to the trial procedures or attend study visits (e.g. major psychiatric condition, dementia).
• Women of child bearing potential should be on a medically accepted form of contraception (oral or implanted contraception, IUD or tubal sterilisation). If there is any possibility of pregnancy, prior to randomisation a blood or urine pregnancy test will be performed. Final decisions about eligibility will be made at the discretion of the trial Investigator and potential trial participant, in light of any additional requirements or guidance from local ethics committees and other regulatory bodies.
• Night shift worker
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-001120-38-NL |
| ClinicalTrials.gov | NCT01506505 |
| CCMO | NL39698.041.12 |