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Strategy for Preventing Cardiovascular and Renal Events Based on ARTErial Stiffness (SPARTE)

Primary Purpose

Hypertension

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Cardiovascular risk management based on PWV
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hypertension focused on measuring arterial stiffness, cardiovascular risk, cardiovascular events, renal events

Eligibility Criteria

55 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • registration to the French social security system
  • patients who did not specifically express their non willingness to participate

PLUS either A, B or C:

  1. Patients with essential hypertension, aged 55 to 75 years old, both sexes

    • Grade 1 hypertension of more
    • Treated or not
    • Whatever the control of BP
    • Under primary of secondary prevention (more than 3 months stroke or myocard infarctus (MI), or stable angina or peripheral artery disease) PLUS at least 3 CV risk factors according to ESH-ESC 2007 guidelines or metabolic syndrome associating at least 2 of the following criteria

      • SBP/DBP over 130/85 mmHg
      • HDL-C <1.0 mmol/l (0,4 g/l) (M) or < 1.2 mmol/l (0,46 g/l) (F)
      • Triglycerides >1,7 mmol/l (>1,5 g/l)
      • Fasting blood glucose 5,6 - 6,9 mmol/l (1,02-1,25 g/l)
      • Waist circumference > 102 cm (M) ou 88 cm (F) or Type 2 diabetes or Target organ damage, according to the definition of the ESH-ESC Guidelines for the Management of Hypertension or CV disease or chronic kidney disease
  2. SBP > 180 mmHg and/or DBP > 110 mmHg
  3. SBP > 160 mmHg AND DBP < 70 mmHg

Exclusion Criteria:

  • Patients with ABPM or self-measurement normal without treatment (<130 mmHg and 80 in the ABPM 24 or <135 and 85 mmHg or daytime ABPM self-measurement of blood pressure)
  • Patients with secondary hypertension (renal artery stenosis, pheochromocytoma, or hypermineralocortisism)
  • Patients with hypertension secondary to diabetic nephropathy
  • Patients aged under 55 or over 75 years,
  • Low-risk CV patients
  • Patients with severe chronic renal impairment creatinine clearance (MDRD) <30ml / min / 1.73m2
  • Patients with type I diabetes
  • Patients with severe disease threatening the vital prognosis in the short and medium terms
  • Patients who previously experienced a painful gynecomastia under spironolactone
  • Patients with alcohol dependence or excessive consumption alcoholic beverages (at the judgement of the investigator)
  • patients with accident history neurovascular, coronary insufficiency (coronary bypass surgery or percutaneous coronary intervention) not older than 3 month
  • Patients with a history of acute heart failure or having open failure heart (NYHA class III-IV)
  • Patients with unstable angina
  • Auricular Fibrillation (AF) less than 6 months ago
  • Patients with aortic stent
  • Patients with known aneurysms of the abdominal aorta
  • Patients with atrioventricular block second or third degree without pacemaker
  • Patients having received organ transplant or placed on a waiting list for transplantation
  • Patients with severe chronic inflammatory disease (rheumatoid arthritis; lupus; scleroderma ...)
  • Patients with severe chronic infectious disease
  • Patients who have had an MI less than 3 months ago
  • Patients with stroke there are less than 3 months ago
  • Patients with progression of peripheral arterial disease
  • Patient whose pregnancy is known or which has no effective contraception if is of childbearing age, or if she is breastfeeding
  • Patients who have expressed their opposition to participate in the protocol or have an inability to understand or follow the protocol
  • The patients geographically too far from the place of investigation
  • Patients already participating in other drug research protocol or Interventional

Sites / Locations

  • Clinical Investigation Center, Hopital Europeen Georges Pompidou

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

PWV group

Conventional group

Arm Description

Cardiovascular risk management based on PWV will include altogether the implementation of international guidelines, the normalisation of blood pressure, and the normalisation of arterial stiffness

These patients will be treated according to the 2007 (and then 2013) ESH-ESC Guidelines for the management of hypertension

Outcomes

Primary Outcome Measures

Number of cardiovascular and renal events
The primary efficacy outcome variable is defined as the composite endpoint of cardiovascular death, non-fatal myocardial Infarction, non-fatal stroke, adverse renal outcome (defined by chronic dialysis, kidney transplantation, or doubling of serum creatinine) and hospitalization for any of the following causes: angioplasty or bypass surgery for coronary or peripheral vessel disease, congestive heart failure, or aortic dissection. An independent committee will validate the events and causes blinded treatment received

Secondary Outcome Measures

Number of non-fatal myocardial Infarction
Number of non-fatal stroke
Number of adverse renal outcome (defined by chronic dialysis, kidney transplantation, or doubling of serum creatinine)
Number of hospitalization for any of the following causes: angioplasty or bypass surgery for coronary or peripheral vessel disease
Number of congestive heart failure
Number of aortic dissection
Carotid-femoral pulse wave velocity (PWV) value at the end of the study
Central systolic blood pressure value
Central pulse pressure value

Full Information

First Posted
September 15, 2015
Last Updated
February 27, 2017
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France, Fondation pour la Recherche en Hypertension Artérielle
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1. Study Identification

Unique Protocol Identification Number
NCT02617238
Brief Title
Strategy for Preventing Cardiovascular and Renal Events Based on ARTErial Stiffness
Acronym
SPARTE
Official Title
Strategy for Preventing Cardiovascular and Renal Events Based on ARTErial Stiffness
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Unknown status
Study Start Date
July 2013 (undefined)
Primary Completion Date
January 2020 (Anticipated)
Study Completion Date
January 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France, Fondation pour la Recherche en Hypertension Artérielle

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Randomised two parallel groups multicenter study using a Prospective Randomised Open Blinded End-point design (PROBE), aiming at comparing the efficacy of a therapeutic strategy targeting the normalisation of arterial stiffness for reducing cardiovascular (CV) and renal events, in comparison with a classical therapeutic strategy implementing the European Society of Hypertension-European Society of Cardiology (ESH-ESC) Guidelines, in patients with essential hypertension and medium-to-very high CV risk.
Detailed Description
The objective is to show that a therapeutic strategy targeting the implementation of international guidelines PLUS the normalisation of blood pression (BP < 140 and 90 mmHg) plus the normalisation of arterial stiffness (measured every 6 months) Pulse Wave Velocity group (PWV group) reduces CV and renal events to a significantly greater extent than the sole implementation of Guidelines (conventional group, with PWV measurement at baseline and every 2 years). Experimental design: Prospective Randomised Open Blinded Endpoint (PROBE) multicenter, two parallel groups, study. Therapeutic strategy in the PWV group: Use maximal recommended doses of angiotensin-converting-enzyme inhibitor (ACEIs) or Angiotensin II receptor blockers (ARBs) as first step treatment. And then adapt treatment to PWV values. In second step, use combination therapy with Calcium channel blockers (CCBs) Use diuretics in combination therapy, either as an alternative to CCBs in second step or as triple therapy in third step Use, as fourth step, vasodilating beta-blockers (VD-BB) or spironolactone In parallel, correct all CV risk factors according to ESH-ESC Guidelines, and reinforce treatment (hypolipidemic drugs, glucose lowering drugs, antiplatelets) if secondary prevention. Therapeutic strategy in the conventional group: Apply the ESH-ESC Guidelines

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
arterial stiffness, cardiovascular risk, cardiovascular events, renal events

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PWV group
Arm Type
Active Comparator
Arm Description
Cardiovascular risk management based on PWV will include altogether the implementation of international guidelines, the normalisation of blood pressure, and the normalisation of arterial stiffness
Arm Title
Conventional group
Arm Type
No Intervention
Arm Description
These patients will be treated according to the 2007 (and then 2013) ESH-ESC Guidelines for the management of hypertension
Intervention Type
Other
Intervention Name(s)
Cardiovascular risk management based on PWV
Intervention Description
Arterial stiffness will be measured through the determination of the carotid-femoral pulse wave velocity (PWV). In the "PWV group", PWV will be measured at baseline, and then every 6 months. PWV measurement will guide the intensification of treatment. Measurements will be immediately available to the physician in charge of the patient, in order to adapt treatment. The therapeutic strategy is based both on the normalisation of BP and then on the BP-independent reduction in PWV, using commercially available antihypertensive medications. In the "conventional group", PWV will be measured at baseline, after 2 years, and at the end of the study. PWV values will be masked to the physician
Primary Outcome Measure Information:
Title
Number of cardiovascular and renal events
Description
The primary efficacy outcome variable is defined as the composite endpoint of cardiovascular death, non-fatal myocardial Infarction, non-fatal stroke, adverse renal outcome (defined by chronic dialysis, kidney transplantation, or doubling of serum creatinine) and hospitalization for any of the following causes: angioplasty or bypass surgery for coronary or peripheral vessel disease, congestive heart failure, or aortic dissection. An independent committee will validate the events and causes blinded treatment received
Time Frame
4 years of follow-up
Secondary Outcome Measure Information:
Title
Number of non-fatal myocardial Infarction
Time Frame
4 years follow-up
Title
Number of non-fatal stroke
Time Frame
4 years follow-up
Title
Number of adverse renal outcome (defined by chronic dialysis, kidney transplantation, or doubling of serum creatinine)
Time Frame
4 years follow-up
Title
Number of hospitalization for any of the following causes: angioplasty or bypass surgery for coronary or peripheral vessel disease
Time Frame
4 years follow-up
Title
Number of congestive heart failure
Time Frame
4 years follow-up
Title
Number of aortic dissection
Time Frame
4 years follow-up
Title
Carotid-femoral pulse wave velocity (PWV) value at the end of the study
Time Frame
4 years follow-up
Title
Central systolic blood pressure value
Time Frame
4 years follow-up
Title
Central pulse pressure value
Time Frame
4 years follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: registration to the French social security system patients who did not specifically express their non willingness to participate PLUS either A, B or C: Patients with essential hypertension, aged 55 to 75 years old, both sexes Grade 1 hypertension of more Treated or not Whatever the control of BP Under primary of secondary prevention (more than 3 months stroke or myocard infarctus (MI), or stable angina or peripheral artery disease) PLUS at least 3 CV risk factors according to ESH-ESC 2007 guidelines or metabolic syndrome associating at least 2 of the following criteria SBP/DBP over 130/85 mmHg HDL-C <1.0 mmol/l (0,4 g/l) (M) or < 1.2 mmol/l (0,46 g/l) (F) Triglycerides >1,7 mmol/l (>1,5 g/l) Fasting blood glucose 5,6 - 6,9 mmol/l (1,02-1,25 g/l) Waist circumference > 102 cm (M) ou 88 cm (F) or Type 2 diabetes or Target organ damage, according to the definition of the ESH-ESC Guidelines for the Management of Hypertension or CV disease or chronic kidney disease SBP > 180 mmHg and/or DBP > 110 mmHg SBP > 160 mmHg AND DBP < 70 mmHg Exclusion Criteria: Patients with ABPM or self-measurement normal without treatment (<130 mmHg and 80 in the ABPM 24 or <135 and 85 mmHg or daytime ABPM self-measurement of blood pressure) Patients with secondary hypertension (renal artery stenosis, pheochromocytoma, or hypermineralocortisism) Patients with hypertension secondary to diabetic nephropathy Patients aged under 55 or over 75 years, Low-risk CV patients Patients with severe chronic renal impairment creatinine clearance (MDRD) <30ml / min / 1.73m2 Patients with type I diabetes Patients with severe disease threatening the vital prognosis in the short and medium terms Patients who previously experienced a painful gynecomastia under spironolactone Patients with alcohol dependence or excessive consumption alcoholic beverages (at the judgement of the investigator) patients with accident history neurovascular, coronary insufficiency (coronary bypass surgery or percutaneous coronary intervention) not older than 3 month Patients with a history of acute heart failure or having open failure heart (NYHA class III-IV) Patients with unstable angina Auricular Fibrillation (AF) less than 6 months ago Patients with aortic stent Patients with known aneurysms of the abdominal aorta Patients with atrioventricular block second or third degree without pacemaker Patients having received organ transplant or placed on a waiting list for transplantation Patients with severe chronic inflammatory disease (rheumatoid arthritis; lupus; scleroderma ...) Patients with severe chronic infectious disease Patients who have had an MI less than 3 months ago Patients with stroke there are less than 3 months ago Patients with progression of peripheral arterial disease Patient whose pregnancy is known or which has no effective contraception if is of childbearing age, or if she is breastfeeding Patients who have expressed their opposition to participate in the protocol or have an inability to understand or follow the protocol The patients geographically too far from the place of investigation Patients already participating in other drug research protocol or Interventional
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephane LAURENT, MD, PhD
Organizational Affiliation
Hopital Europen Georges Pompidou, Assistance publique Hopitaux de Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pierre BOUTOUYRIE, MD, PhD
Organizational Affiliation
Hopital Europen Georges Pompidou, Assistance publique Hopitaux de Paris
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Investigation Center, Hopital Europeen Georges Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
22733473
Citation
Laurent S, Briet M, Boutouyrie P. Arterial stiffness as surrogate end point: needed clinical trials. Hypertension. 2012 Aug;60(2):518-22. doi: 10.1161/HYPERTENSIONAHA.112.194456. Epub 2012 Jun 25. No abstract available.
Results Reference
background
PubMed Identifier
17000623
Citation
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H; European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006 Nov;27(21):2588-605. doi: 10.1093/eurheartj/ehl254. Epub 2006 Sep 25.
Results Reference
background
PubMed Identifier
17563527
Citation
Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007 Jun;25(6):1105-87. doi: 10.1097/HJH.0b013e3281fc975a. No abstract available. Erratum In: J Hypertens. 2007 Aug;25(8):1749.
Results Reference
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Strategy for Preventing Cardiovascular and Renal Events Based on ARTErial Stiffness

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