- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01506505
The Evening Versus Morning Polypill Utilization Study (TEMPUS)
A Randomised Controlled Cross-over Trial to Evaluate Evening Versus Morning Administration of a Cardiovascular Polypill
Background and rationale:
In clinical practice, antihypertensives 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 cholesterol achieved with some statins is superior when taken in the night, but it is unclear whether the additional reduction in LDL cholesterol(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. Current product labelling recommends night use for simvastatin and does not state a timing preference for aspirin or blood pressure lowering medicines. There is therefore uncertainty concerning the best timing of administration of the polypill. This uncertainty will be addressed by this trial.
Trial design:
Randomised, open label cross over trial (n=75) of the polypill in the morning compared with the evening administration compared with individual agent administration (acetylsalicylic acid and blood pressure lowering agents in the morning, and statin in the evening) in individuals at high risk of cardiovascular disease. Patients will be recruited to the RHP 2c (acetylsalicylic acid 75mg, simvastatin 40mg, lisinopril 10mg, hydrochlorthiazide 12.5mg), and will be randomly allocated to the sequence of time of administration.
Study Overview
Status
Intervention / Treatment
Detailed Description
Background and rationale:
In clinical practice, antihypertensives 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 cholesterol achieved with some statins is superior when taken in the night, but it is unclear whether the additional reduction in LDL cholesterol(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. Current product labelling recommends night use for simvastatin and does not state a timing preference for aspirin or blood pressure lowering medicines. There is therefore uncertainty concerning the best timing of administration of the polypill. This uncertainty will be addressed by this trial.
Trial design:
Randomised, open label cross over trial (n=75) of the polypill in the morning compared with the evening administration compared with individual agent administration (acetylsalicylic acid and blood pressure lowering agents in the morning, and statin in the evening) in individuals at high risk of cardiovascular disease. Patients will be recruited to the RHP 2c (acetylsalicylic acid 75mg, simvastatin 40mg, lisinopril 10mg, hydrochlorthiazide 12.5mg), and will be randomly allocated to the sequence of time of administration.
Aim:
To measure whether there is a difference in LDL cholesterol levels or the 24 hour ambulatory blood pressure in individuals at high risk of cardiovascular disease when the polypill is taken in the morning compared to the evening.
Randomisation and trial treatment:
Eligible individuals willing to participate in the trial will receive the polypill for a total of 18 weeks and be randomised to the sequence of 6 weeks morning, 6 weeks evening administration and 6 weeks administration of the individual agents. The polypill will be provided by the investigator at the Trial Centre. Participants will also receive information about smoking cessation (if applicable) and how to follow a healthy heart diet. They will be advised to increase physical activity and lose weight if needed.
Data collection and follow-up:
Participants will be followed-up for 20 weeks. Ambulatory blood pressure will be measured at baseline and week 6, week 12 and week 18. Fasting lipids will be measured at baseline, weeks 6, 12 and 18. Tolerability will be assessed at weeks 6, 12, 18 and 20 as will adverse events. Participant acceptability will be measured at the end of the treatment period.
Primary outcome:
Difference in LDL cholesterol and mean 24 hour ambulatory systolic BP.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Utrecht, Netherlands, 3508 GA
- UMC Utrecht
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- The participant is able to give informed consent.
- The trial Investigator considers that each of the polypill components are indicated at the doses in the Red Heart Pill
Established atherothrombotic cardiovascular disease (CVD) or intermediate to high cardiovascular risk, defined as;
- History of coronary heart disease (myocardial infarction, stable or unstable angina pectoris, or coronary revascularisation procedure), or
- History of ischaemic cerebrovascular disease (ischaemic stroke or transient ischaemic attack), or
- History of peripheral vascular disease (peripheral revascularisation procedure or amputation due to vascular disease or aortic reconstruction), or
- For individuals without established cardiovascular disease, a calculated 5 year CVD risk of 5% or greater (calculated using the 1991 Anderson Framingham risk equation with adjustments as defined by the New Zealand Guidelines Group recommendations - (Appendix 1))
Exclusion Criteria:
- 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 contraindications are fully listed in the Investigator Brochures.
- The treating 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, 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).
- Any reason, medical condition, ongoing medication or significant disability that would prevent the participant complying with trial consent, treatment and follow-up procedures or potentially jeopardise her / his medical care.
- Night shift workers.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Polypill in the morning
Cardiovascular agents in a polypill used from 05.00-11.00 in the morning (acetylsalicylic acid 75 mg, simvastatin 40 mg, lisinopril 10 mg, hydrochlorothiazide 12,5 mg)
|
Acetylsalicylic acid 75mg, simvastatin 40mg, lisinopril 10mg, hydrochlorthiazide 12.5mg in individual agents or a combination pill
Other Names:
|
Experimental: Polypill in the evening
Cardiovascular agents in a polypill used from 18.00-00.00 in the evening (acetylsalicylic acid 75 mg, simvastatin 40 mg, lisinopril 10 mg, hydrochlorothiazide 12,5 mg)
|
Acetylsalicylic acid 75mg, simvastatin 40mg, lisinopril 10mg, hydrochlorthiazide 12.5mg in individual agents or a combination pill
Other Names:
|
Active Comparator: Individual agents of the polypill)
Cardiovascular agents in as acetylsalicylic acid 75 mg, lisinopril 10 mg, hydrochlorothiazide 12,5 mg used 05.00-11.00 in the morning. Simvastatin 40 mg used 18.00-00.00 in the evening. |
Acetylsalicylic acid 75mg, simvastatin 40mg, lisinopril 10mg, hydrochlorthiazide 12.5mg in individual agents or a combination pill
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
LDL cholesterol (polypill evening vs polypill morning)
Time Frame: 24 weeks
|
Differences between polypill in the evening (after 8 weeks of evening treatment) and polypill in the morning (after 8 weeks of morning treatment) in: - Mean LDL cholesterol |
24 weeks
|
Mean 24 hour ambulatory systolic BP (polypill evening vs morning)
Time Frame: 24 weeks
|
Difference between the between polypill in the evening (after 8 weeks of evening treatment) and polypill in the morning (after 8 weeks of morning treatment) in: - Mean 24 hour ambulatory systolic BP |
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Differences in ambulatory BP parameters after a mean of 7 week of treatment (polypill evening vs. morning, polypill vs regular care)
Time Frame: 24 weeks
|
Differences between polypill in the evening (after 8 weeks of evening treatment) and polypill in the morning (after 8 weeks of morning treatment) and regular care (after 8 weeks of treatment with individual agents of the polypill) in:
|
24 weeks
|
Differences in tolerability (adverse event, cessation of treatment)
Time Frame: Every 6-8 weeks
|
Difference between polypill in the evening (after 8 weeks of evening treatment) and polypill in the morning (after 8 weeks of morning treatment) and regular care (after 8 weeks of treatment with individual agents of the polypill) in:
|
Every 6-8 weeks
|
Adherence (polypill evening vs. morning, polypill vs regular care)
Time Frame: 24 weeks
|
Differences between polypill in the evening (after 8 of evening treatment) and polypill in the morning (after 8 weeks of morning treatment) and regular care (after 8 weeks of treatment with individual agents of the polypill) in:
|
24 weeks
|
Cholesterol fractions (polypill evening vs. morning, polypill vs regular care)
Time Frame: 24 weeks
|
Differences between polypill in the evening (after 8 of evening treatment) and polypill in the morning (after 8 weeks of morning treatment) and regular care (after 8 weeks of treatment with individual agents of the polypill) in:
|
24 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: W. Spiering, MD, PhD, UMC Utrecht
Publications and helpful links
General Publications
- Lafeber M, Grobbee DE, Schrover IM, Thom S, Webster R, Rodgers A, Visseren FL, Bots ML, Spiering W. Comparison of a morning polypill, evening polypill and individual pills on LDL-cholesterol, ambulatory blood pressure and adherence in high-risk patients; a randomized crossover trial. Int J Cardiol. 2015 Feb 15;181:193-9. doi: 10.1016/j.ijcard.2014.11.176. Epub 2014 Dec 3.
- Lafeber M, Grobbee DE, Bots ML, Thom S, Webster R, Rodgers A, Visseren FL, Spiering W. The evening versus morning polypill utilization study: the TEMPUS rationale and design. Eur J Prev Cardiol. 2014 Apr;21(4):425-33. doi: 10.1177/2047487313476961. Epub 2013 Feb 4.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Atherosclerosis
- Cardiovascular Diseases
- Peripheral Arterial Disease
- Peripheral Vascular Diseases
- Cerebrovascular Disorders
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Cyclooxygenase Inhibitors
- Antipyretics
- Antimetabolites
- Protease Inhibitors
- Protective Agents
- Natriuretic Agents
- Cardiotonic Agents
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Membrane Transport Modulators
- Diuretics
- Angiotensin-Converting Enzyme Inhibitors
- Sodium Chloride Symporter Inhibitors
- Aspirin
- Hydrochlorothiazide
- Simvastatin
- Lisinopril
Other Study ID Numbers
- EudraCT 2011-001120-38
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cardiovascular Disease
-
University of FloridaUniversity of Alabama at Birmingham; Brown UniversityCompletedCardiovascular Disease | Psychosocial Influence on Cardiovascular DiseaseUnited States
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedCardiovascular Disease | Inflammatory DiseaseUnited States
-
Morehouse School of MedicineNot yet recruiting
-
Yonsei UniversityRecruitingCardiovascular DiseaseKorea, Republic of
-
Nanjing Medical UniversityNot yet recruitingCardiovascular Disease
-
National Human Genome Research Institute (NHGRI)Active, not recruiting
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruiting
-
AmgenCompletedCardiovascular DiseaseUnited States, Australia
-
VA Office of Research and DevelopmentEnrolling by invitationCardiovascular DiseaseUnited States
Clinical Trials on Cardiovascular Agents
-
Hospital Parc Taulí, SabadellUnknownCardiovascular Disease | Osteoarthritis | Metabolic Syndrome | Cardiovascular Risk FactorsSpain
-
University Hospital, EssenCompletedCardiovascular Diseases | Cardiovascular Risk Factor | SARSGermany
-
Klaus Fuglsang KofoedHerlev HospitalActive, not recruitingCardiovascular Diseases | Atherosclerosis | Pre-Eclampsia | Heart Disease in WomenDenmark
-
Charles University, Czech RepublicActive, not recruitingCardiovascular Diseases | Hypertension | Arterial StiffnessCzechia
-
University Hospital, LimogesTerminated
-
Universidade Estadual Paulista Júlio de Mesquita...Fundação de Amparo à Pesquisa do Estado de São PauloUnknownCardiovascular Diseases | Cardiovascular Risk Factor
-
Apica Cardiovascular LimitedCompleted
-
Balgrist University HospitalUniversity of ZurichTerminatedCardiovascular DiseaseSwitzerland
-
Tianjin Medical University General HospitalUnknownCardiovascular Disease | AtherosclerosisChina
-
University of LeicesterRecruiting