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Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment (HYGIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00741585
Recruitment Status : Completed
First Posted : August 26, 2008
Last Update Posted : August 28, 2018
Sponsor:
Collaborator:
Servicio Gallego de Salud
Information provided by (Responsible Party):
Ramon C. Hermida, University of Vigo

Tracking Information
First Submitted Date  ICMJE August 25, 2008
First Posted Date  ICMJE August 26, 2008
Last Update Posted Date August 28, 2018
Actual Study Start Date  ICMJE September 1, 2008
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
To evaluate the impact of circadian time of treatment in cardiovascular, cerebrovascular, metabolic, and renal risk assessment. [ Time Frame: Yearly evaluation for at least ten years ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 25, 2008)
To evaluate the prognostic value of ABPM, the impact of changes in ambulatory BP and the impact of circadian time of treatment in cardiovascular, cerebrovascular and renal risk assessment. [ Time Frame: Ten years ]
Change History Complete list of historical versions of study NCT00741585 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
  • To evaluate the influence of circadian time of treatment in BP control of hypertensive patients. [ Time Frame: Yearly evaluation for at least ten years ]
  • To evaluate the prevalence of an altered (non-dipper) BP profile in patients with resistant hypertension as a function of the circadian time of treatment. [ Time Frame: Yearly evaluation for at least ten years ]
  • To evaluate the influence of diabetes and circadian time of treatment in the prevalence of an altered (non-dipper) BP profile. [ Time Frame: Yearly evaluation for at least ten years ]
  • To evaluate the influence of age and circadian time of treatment in the prevalence of an altered (non-dipper) BP profile. [ Time Frame: Yearly evaluation for at least ten years ]
  • To evaluate, for all groups of interest, the prevalence and vascular, metabolic, and renal risk profile of white-coat hypertension. [ Time Frame: Yearly evaluation for at least ten years ]
  • To evaluate, for all groups of interest, the prevalence and vascular, metabolic, and renal risk profile of masked hypertension. [ Time Frame: Yearly evaluation for at least ten years ]
  • To evaluate, for all previous objectives, potential differences between men and women. [ Time Frame: Yearly evaluation for at least ten years ]
  • To evaluate the impact of changes in ambulatory BP in vascular, metabolic, and renal risk assessment. [ Time Frame: Yearly evaluation for at least ten years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2008)
  • To evaluate the influence of circadian time of treatment in BP control and the remodeling of the circadian BP pattern of hypertensive patients. [ Time Frame: Ten years ]
  • To evaluate the prevalence of an altered (non-dipper) BP profile in patients with resistant hypertension as a function of the circadian time of treatment. [ Time Frame: Ten years ]
  • To evaluate the influence of diabetes, presence of treatment, and the circadian time of treatment in the prevalence of an altered (non-dipper) BP profile. [ Time Frame: Ten years ]
  • To evaluate the influence of age, presence of treatment, and the circadian time of treatment in the prevalence of an altered (non-dipper) BP profile. [ Time Frame: Ten years ]
  • To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of white-coat hypertension. [ Time Frame: Ten years ]
  • To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of masked hypertension. [ Time Frame: Ten years ]
  • To evaluate, for all previous objectives, potential differences between men and women. [ Time Frame: Ten years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment
Official Title  ICMJE Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment
Brief Summary

The HYGIA study was designed to investigate prospectively

  1. the prognostic value of ambulatory blood pressure (BP) monitoring among subjects primarily evaluated at primary care settings
  2. the impact of changes in ambulatory BP during follow-up in cardiovascular, cerebrovascular, metabolic, and renal risk in hypertensive patients
  3. the influence of circadian time of treatment in cardiovascular, cerebrovascular, metabolic, and renal risk in hypertensive patients
  4. the prevalence of an altered BP profile as a function of antihypertensive treatment, circadian time of treatment, age, and presence of diabetes, among other factors.
Detailed Description

Ambulatory blood pressure (BP) measurements (ABPM) correlate more closely with target organ damage and cardiovascular events than clinical cuff measurements. ABPM reveals the significant circadian variation in BP, which in most individuals presents a morning increase, small post-prandial decline, and more extensive lowering during nocturnal rest. However, under certain pathophysiological conditions, the nocturnal BP decline may be reduced (non-dipper pattern) or even reversed (riser pattern). This is clinically relevant since the non-dipper and riser circadian BP patterns constitute a risk factor for left ventricular hypertrophy, albuminuria, cerebrovascular disease, congestive heart failure, vascular dementia, and myocardial infarction. Hence, there is growing interest in how to best tailor and individualize the treatment of hypertension according to the specific circadian BP pattern of each patient.

The reduction of the normal 10-20% sleep-time BP decline that is characteristic of the non-dipper and riser patterns is indeed associated with elevated risk of target organ damage, particularly to the heart (left ventricular hypertrophy, congestive heart failure, and myocardial infarction), brain (stroke), and kidney (albuminuria and progression to end-stage renal failure). These results suggest that cardiovascular risk could be influenced not by BP elevation alone, but also by the magnitude of the circadian BP variability. However, the potential dimension of an altered BP profile is still under debate, as there is current discrepancy on the actual prevalence of a non-dipper BP profile among groups of interest, mainly the elderly, patients with diabetes and patients with resistant hypertension.

Moreover, several independent prospective studies have suggested that nighttime BP may be a better predictor of cardiovascular 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. Moreover, the potential benefit, i.e., reduction in cardiovascular risk, associated with the normalization of the circadian BP variability (e.g., conversion from non-dipper to dipper pattern) from appropriately envisioned treatment strategy is still a matter of debate.

The HYGIA study was designed to investigate, first, the comparative prognostic value of several BP parameters (including, among many others, BP variability, the diurnal/nocturnal ratio, diurnal and nocturnal means, hyperbaric index, slope of morning rise, etc) in the prediction of vascular, metabolic, and renal morbidity and mortality; second, whether potential changes in the circadian BP pattern after treatment with hypertension medications may be associated to changes in the risk of cardiovascular events, stroke, diabetes, and/or chronic kidney disease; and third, in keeping with the second major objective above, to further assess the potential changes in efficacy, safety profile, and/or capability of hypertension medications, used either alone or in combination, to modulate the circadian BP pattern and to reduce vascular, metabolic, and renal risks as a function of the circadian time of administration.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Essential Hypertension
  • Cardiovascular Disease
  • Stroke
  • Chronic Kidney Disease
Intervention  ICMJE
  • Drug: Any antihypertensive medication alone or in combination
    All drugs on awakening
    Other Names:
    • Olmesartan
    • Irbesartan
    • Candesartan
    • Telmisartan
    • Valsartan
    • Atenolol
    • Carvedilol
    • Nevibolol
    • Doxazosine
    • Lercanidipine
    • Manidipine
    • Amlodipine
    • Ramipril
    • Enalapril
    • Lisinopril
    • Quinapril
  • Drug: Any antihypertensive medication alone or in combination
    One or more drugs at bedtime
    Other Names:
    • Olmesartan
    • Irbesartan
    • Candesartan
    • Telmisartan
    • Valsartan
    • Atenolol
    • Carvedilol
    • Nevibolol
    • Doxazosine
    • Lercanidipine
    • Manidipine
    • Amlodipine
    • Ramipril
    • Enalapril
    • Lisinopril
    • Quinapril
  • Device: Ambulatory blood pressure monitoring
    Sampling at 20-min intervals from 07:00 to 23:00 and at 30-min intervals at night for 48 consecutive hours
    Other Name: ABPM
Study Arms  ICMJE
  • Active Comparator: 1
    Treatment with all prescribed hypertension medications on awakening
    Interventions:
    • Drug: Any antihypertensive medication alone or in combination
    • Device: Ambulatory blood pressure monitoring
  • Active Comparator: 2
    Treatment with at least one prescribed hypertension medication at bedtime
    Interventions:
    • Drug: Any antihypertensive medication alone or in combination
    • Device: Ambulatory blood pressure monitoring
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 24, 2018)
21983
Original Estimated Enrollment  ICMJE
 (submitted: August 25, 2008)
5000
Actual Study Completion Date  ICMJE June 30, 2018
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female subjects ≥18 years of age.
  • High-normal BP or essential hypertension.
  • Any subject with recommendation for evaluation with ABPM according to the 2007 European Guidelines.
  • Informed consent to participate in the study prior to any study procedures.

Exclusion Criteria:

  • Known or suspected contraindications to any potential medication under investigation.
  • Shift-workers.
  • Inability to communicate and comply with all study requirements.
  • Persons directly involved in the execution of this protocol.
  • Intolerants to the use of the ABPM device.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00741585
Other Study ID Numbers  ICMJE HYGIA
Hygia-2007-440
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ramon C. Hermida, University of Vigo
Study Sponsor  ICMJE University of Vigo
Collaborators  ICMJE Servicio Gallego de Salud
Investigators  ICMJE
Study Director: Ramon C Hermida, PhD University of Vigo
PRS Account University of Vigo
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP