Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy (MAPEC)

• ClinicalTrials.gov Identifier: NCT00295542
• Recruitment Status: Completed
• First Posted: February 23, 2006
• Last Update Posted: April 28, 2009
• Sponsor: University of Vigo
• Collaborators: Hospital Clinico Universitario de Santiago; Xunta de Galicia; Ministerio de Educacion y Ciencia, Spain
• Information provided by: University of Vigo

Tracking Information

• First Submitted Date: February 21, 2006
• First Posted Date: February 23, 2006
• Last Update Posted Date: April 28, 2009
• Study Start Date: March 2000
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 2, 2008): Prognostic value of ABPM, impact of changes in ambulatory BP and impact of circadian time of antihypertensive treatment in cardiovascular, cerebrovascular and renal risk assessment. [ Time Frame: Five years ]

Original Primary Outcome Measures (submitted: February 22, 2006)

• circadian pattern of blood pressure determined by ambulatory monitoring
• cardiovascular and cerebrovascular events per year of follow-up
• total cardiovascular mortality per year of follow-up

Current Secondary Outcome Measures (submitted: September 2, 2008)

• Influence of circadian time of antihypertensive treatment in BP control and the remodeling of the circadian BP pattern of hypertensive patients. [ Time Frame: Five years ]
• Prevalence of an altered BP profile as a function of the circadian time of treatment. [ Time Frame: Five years ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy
• Official Title: Prognostic Value of Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy in Relation to Risk (the MAPEC Study).
• Brief Summary: The MAPEC study was designed to investigate whether normalizing the circadian blood pressure profile towards a more dipper pattern (increasing the diurnal/nocturnal ratio of blood pressure) by the use of Chronotherapy (that is, taking into account the time of day of administration of antihypertensive medications) reduces cardiovascular risk.
• Detailed Description: Target organ damage is more closely associated with ambulatory (ABPM) than with clinic blood pressure (BP). In particular, the reduction of the normal 10 to 20% sleep-time BP decline (non-dipper pattern) is associated with elevated risk of end-organ injury, particularly to the heart, brain and kidney. These results suggest that cardiovascular risk could be influenced not by BP elevation alone, but also by the magnitude of the circadian BP variability. Moreover, at least two independent prospective studies have suggested that nighttime BP is a better predictor of risk than daytime BP. Common to all previous trials is that prognostic significance of ABPM has relied on a single baseline profile from each participant, without accounting for possible changes in the BP pattern, mainly associated to antihypertensive therapy and aging during follow-up. The MAPEC study investigates, first, the comparative prognostic value of several BP parameters (including, among many others, BP variability, the diurnal/nocturnal ratio, diurnal and nocturnal means, slope of morning rise, etc) in the prediction of cardiovascular morbidity and mortality; and, second, whether potential changes in the circadian BP pattern after Chronotherapy with antihypertensive drugs are associated to changes in cardiovascular risk.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• Device: Ambulatory blood pressure monitoring
  Sampling at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours
• Procedure: Chronotherapy, timing of antihypertensive medication
  Comparison of effects of awakening versus bedtime dosing
• Drug: ACEI (including spirapril, enalapril, quinapril, lisinopril)
  Treatment at awakening versus bedtime
• Drug: ARB (including valsartan, telmisartan, olmesartan)
  Treatment at awakening versus bedtime
• Drug: beta blockers (including nebivolol, atenolol, carvedilol)
  Treatment at awakening versus bedtime
• Drug: diuretics (torasemide, indapamide, HTCZ) and doxazosin
  Treatment at awakening versus bedtime
• Procedure: Combination therapy in essential hypertension
  Treatment at awakening versus bedtime

Study Arms

• Active Comparator: 1
  Treatment on awakening
  Interventions:

  • Device: Ambulatory blood pressure monitoring
  • Procedure: Chronotherapy, timing of antihypertensive medication
  • Drug: ACEI (including spirapril, enalapril, quinapril, lisinopril)
  • Drug: ARB (including valsartan, telmisartan, olmesartan)
  • Drug: beta blockers (including nebivolol, atenolol, carvedilol)
  • Drug: diuretics (torasemide, indapamide, HTCZ) and doxazosin
  • Procedure: Combination therapy in essential hypertension
• Active Comparator: 2
  Treatment at bedtime
  Interventions:

  • Device: Ambulatory blood pressure monitoring
  • Procedure: Chronotherapy, timing of antihypertensive medication
  • Drug: ACEI (including spirapril, enalapril, quinapril, lisinopril)
  • Drug: ARB (including valsartan, telmisartan, olmesartan)
  • Drug: beta blockers (including nebivolol, atenolol, carvedilol)
  • Drug: diuretics (torasemide, indapamide, HTCZ) and doxazosin
  • Procedure: Combination therapy in essential hypertension

Publications *

• Hermida RC, Ayala DE, Mojon A, Fernandez JR. Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial. Diabetologia. 2016 Feb;59(2):255-65. doi: 10.1007/s00125-015-3749-7. Epub 2015 Sep 23. Erratum In: Diabetologia. 2016 Feb;59(2):395.
• Hermida RC, Ayala DE, Mojon A, Fernandez JR. Decreasing sleep-time blood pressure determined by ambulatory monitoring reduces cardiovascular risk. J Am Coll Cardiol. 2011 Sep 6;58(11):1165-73. doi: 10.1016/j.jacc.2011.04.043.
• Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care. 2011 Jun;34(6):1270-6. doi: 10.2337/dc11-0297.
• Hermida RC, Ayala DE, Mojon A, Fernandez JR. Ambulatory blood pressure control with bedtime aspirin administration in subjects with prehypertension. Am J Hypertens. 2009 Aug;22(8):896-903. doi: 10.1038/ajh.2009.83. Epub 2009 Apr 30.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 2, 2009): 3344
• Original Enrollment (submitted: February 22, 2006): 3000
• Actual Study Completion Date: April 2009
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Essential hypertension

Exclusion Criteria:

• AIDS
• shift workers
• secondary hypertension
• intolerant to ABPM

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT00295542
• Other Study ID Numbers: PGIDIT03-PXIB-32201PR; SAF2006-6254; INCITE07-PXI-322003ES
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ramon C. Hermida, University of Vigo
• Original Responsible Party: Not Provided
• Current Study Sponsor: University of Vigo
• Original Study Sponsor: Same as current

Collaborators

• Hospital Clinico Universitario de Santiago
• Xunta de Galicia
• Ministerio de Educacion y Ciencia, Spain

Investigators

• Principal Investigator: Ramon C Hermida, PhD; University of Vigo

• PRS Account: University of Vigo
• Verification Date: April 2009