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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Vigo
Sponsor:
Collaborator:
Servicio Gallego de Salud
Information provided by (Responsible Party):
Ramon C. Hermida, University of Vigo
ClinicalTrials.gov Identifier:
NCT00741585
First received: August 25, 2008
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

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 and renal risk in hypertensive patients
  3. the influence of circadian time of treatment in cardiovascular, cerebrovascular 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.

Condition Intervention Phase
Essential Hypertension
Cardiovascular Disease
Stroke
Chronic Kidney Disease
Drug: Any antihypertensive medication alone or in combination
Device: Ambulatory blood pressure monitoring
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Cardiovascular Risk Assessment

Resource links provided by NLM:


Further study details as provided by University of Vigo:

Primary Outcome Measures:
  • To evaluate the impact of circadian time of treatment in cardiovascular, cerebrovascular and renal risk assessment. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the influence of circadian time of treatment in BP control of hypertensive patients. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of white-coat hypertension. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  • To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of masked hypertension. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  • To evaluate, for all previous objectives, potential differences between men and women. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  • To evaluate the impact of changes in ambulatory BP in cardiovascular, cerebrovascular and renal risk assessment. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 12000
Study Start Date: January 2008
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Treatment with all prescribed hypertension medications on awakening
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
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
Active Comparator: 2
Treatment with at least one prescribed hypertension medication at bedtime
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

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, microalbuminuria, 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 (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 cardiovascular morbidity and mortality; second, whether potential changes in the circadian BP pattern after treatment with antihypertensive medications may be associated to changes in the risk of cardiovascular events, stroke, 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 antihypertensive medication, used either alone or in combination, to modulate the circadian BP pattern as a function of the circadian time of administration.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00741585

Contacts
Contact: Ramon C Hermida, PhD 34986812148 rhermida@uvigo.es
Contact: Diana E Ayala, MD, PhD 34986812148 dianaelva@hotmail.com

Locations
Spain
CS Friol Recruiting
Friol, Lugo, Spain, 27220
Contact: Esther Gomez, MD    34639512093    Esther.Gomez.Sal@sergas.es   
Principal Investigator: Esther Gomez, MD         
CS Bayona Recruiting
Bayona, Pontevedra, Spain, 36300
Contact: Francisco J Iglesias, MD    34986357239    FranciscoJavier.Iglesias.Mato@sergas.es   
Principal Investigator: Francisco J Iglesias, MD         
CS Bueu Recruiting
Bueu, Pontevedra, Spain, 36930
Contact: Miguel A Aboal, MD    34986323313    miguel.angel.aboal.beato@sergas.es   
Principal Investigator: Miguel A Aboal, MD         
CS A Estrada Recruiting
La Estrada, Pontevedra, Spain, 26680
Contact: Luis Meijide, MD    34986573459    Luis.Meijide.Calvo@sergas.es   
Principal Investigator: Luis Meijide, MD         
Sub-Investigator: Mariana Carbon, MD         
Sub-Investigator: Maria C Garcia, MD         
Sub-Investigator: Francisco Romero, MD         
Sub-Investigator: Maria P Brea         
CS A Guarda Recruiting
La Guardia, Pontevedra, Spain, 36780
Contact: Juan J Crespo, MD    34986614450    JuanJose.Crespo.Sabaris@sergas.es   
Principal Investigator: Juan J Crespo, MD         
Sub-Investigator: Raquel Fernandez, MD         
Sub-Investigator: Carmen M Fernandez, MD         
Sub-Investigator: Amelia Ferreras, MD         
Sub-Investigator: Manuel Quintans, MD         
Sub-Investigator: Javier Rodriguez, MD         
Sub-Investigator: Pilar Rua, MD         
Sub-Investigator: Aurelio Alvarez         
Sub-Investigator: Asuncion Cadilla         
Sub-Investigator: Carmen Outeiro         
Sub-Investigator: Carmen Soto-Davila         
CS Valmiñor Recruiting
Nigran, Pontevedra, Spain, 36250
Contact: Susana Hernaiz, MD    34655391498    Susana.Hernaiz.Valero@sergas.es   
Principal Investigator: Susana Hernaiz, MD         
CS Panxón Recruiting
Nigrán, Pontevedra, Spain, 36340
Contact: Jose L Salgado, MD    34986368615    joseluis.salgado.conde@sergas.es   
Principal Investigator: Jose L Salgado, MD         
Sub-Investigator: Esperanza Parrado         
Sub-Investigator: Alfredo Pereira         
CS Tomiño Recruiting
Tomiño, Pontevedra, Spain, 36200
Contact: Evangelina Filloy, MD    34-986-623411    evangelina.filloy.miguez@sergas.es   
Principal Investigator: Evangelina Filloy, MD         
Sub-Investigator: Adolfo T Perez, MD         
Sub-Investigator: Nieves Turienzo, MD         
Sub-Investigator: Dolores Cardalda         
Sub-Investigator: Jose C Varela         
Sub-Investigator: Francisca Vazquez         
Hospital do Meixoeiro Recruiting
Vigo, Pontevedra, Spain, 36200
Contact: Roberto Perez, MD    34627517077    roberto.perez.alvarez@sergas.es   
Principal Investigator: Roberto Perez, MD         
Bioengineering & Chronobilogy Labs., University of Vigo Recruiting
Vigo, Pontevedra, Spain, 36200
Contact: Ramon C Hermida, PhD    34986812148    rhermida@uvigo.es   
Contact: Diana E Ayala, MD, PhD    34986812148    dianaelva@uvigo.es   
Principal Investigator: Ramon C Hermida, PhD         
Principal Investigator: Diana E Ayala, MD, PhD         
Sub-Investigator: Artemio Mojon, PhD         
Sub-Investigator: Jose R Fernandez, PhD         
Sub-Investigator: Ignacio Alonso, PhD         
Sub-Investigator: Maria J Fontao         
Sub-Investigator: Rita Soler         
Sub-Investigator: Susana Serrano         
CS A Doblada Recruiting
Vigo, Pontevedra, Spain, 36205
Contact: Teresa Rios, MD    34986275121    teresa.rios.rey@sergas.es   
Principal Investigator: Teresa Rios, MD         
CS Calle Cuba Recruiting
Vigo, Pontevedra, Spain, 36202
Contact: Felisa Dominguez, MD    34986416226    fdominguez@meditex.es   
Principal Investigator: Felisa Dominguez, MD         
CS Coia Recruiting
Vigo, Pontevedra, Spain, 36209
Contact: Peregrina Eiroa, MD    34986209282    pereeiroa@telefonica.net   
Principal Investigator: Peregrina Eiroa, MD, PhD         
Sub-Investigator: Jesus C Nieto, MD         
CS Teis Recruiting
Vigo, Pontevedra, Spain, 36216
Contact: Pedro A Callejas, MD    34986374229    PedroAntonio.Callejas.Cabanillas@sergas.es   
Principal Investigator: Pedro A Callejas, MD         
CS Sardoma Recruiting
Vigo, Pontevedra, Spain, 36214
Contact: Manuel Dominguez, MD, PhD    34986416324    Manuel.Dominguez.Sardina@sergas.es   
Principal Investigator: Manuel Dominguez, MD, PhD         
CS Vilaboa Recruiting
Vilaboa, Pontevedra, Spain, 36141
Contact: Sonia M Gomara, MD    34986679229    SoniaMaria.Gomara.Villabona@sergas.es   
Principal Investigator: Sonia M Gomara, MD         
Sub-Investigator: Julio J Alvarez, MD         
Sub-Investigator: Margarita Estevez         
Sub-Investigator: Maria C Ferreira         
CS San Roque Recruiting
Villagarcia de Arosa, Pontevedra, Spain, 36600
Contact: Envira Sineiro, MD    34986507448    Elvira.Sineiro.Galinanes@sergas.es   
Principal Investigator: Elvira Sineiro, MD         
Sub-Investigator: Margarita Alvariño         
Sub-Investigator: Luis M Fontenla         
Sub-Investigator: Margarita Fraga, MD         
Sub-Investigator: Barbara Llovo         
Sub-Investigator: Rita Martinez         
Sub-Investigator: Santiago Santidrian, MD         
CS Fingoi Recruiting
Lugo, Spain, 27002
Contact: Carmen Castiñeira, MD    34982251035    Carmen.Castineira.Perez@sergas.es   
Principal Investigator: Carmen Castiñeira, MD         
Sub-Investigator: Maria C Aguado         
Sub-Investigator: Carmen Costa         
Sub-Investigator: Domingo D Garcia, MD         
Sub-Investigator: Bernardino Pardo, MD         
Sub-Investigator: Enrique J Vazquez, MD         
Complexo Hospitalario Universitario de Ourense Recruiting
Orense, Spain, 32005
Contact: Alfonso Otero, MD, PhD    34988385625    Alfonso.Santiago.Otero.Gonzalez@sergas.es   
Principal Investigator: Alfonso Otero, MD, PhD         
CS Lerez Recruiting
Pontevedra, Spain, 36156
Contact: Ana Moya, MD    34986871496    ana.moya.alvarez@sergas.es   
Principal Investigator: Ana Moya, MD         
Sub-Investigator: Andres Ruiz, MD         
Sub-Investigator: Aurelia Constenla         
Sub-Investigator: Maria I Franco         
Sponsors and Collaborators
University of Vigo
Servicio Gallego de Salud
Investigators
Study Director: Ramon C Hermida, PhD University of Vigo
  More Information

Additional Information:
No publications provided

Responsible Party: Ramon C. Hermida, Professor, University of Vigo
ClinicalTrials.gov Identifier: NCT00741585     History of Changes
Other Study ID Numbers: HYGIA, Hygia-2007-440
Study First Received: August 25, 2008
Last Updated: August 22, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by University of Vigo:
Ambulatory blood pressure monitoring
Chronotherapy
Circadian
Non-dipper
Type 2 diabetes
Resistant hypertension
Total mortality

Additional relevant MeSH terms:
Antihypertensive Agents
Hypertension
Cardiovascular Diseases
Kidney Diseases
Renal Insufficiency, Chronic
Vascular Diseases
Urologic Diseases
Renal Insufficiency
Candesartan
Candesartan cilexetil
Olmesartan
Olmesartan medoxomil
Carvedilol
Valsartan
Quinapril
Lercanidipine
Irbesartan
Telmisartan
Ramipril
Lisinopril
Amlodipine
Enalapril
Atenolol
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014