Systolic Hypertension in Europe Placebo-Controlled Trial (Syst-Eur)

Systolic Hypertension in Europe Trial

The Syst-Eur Trial is a concerted action of the European Community's Medical and Health Research Programme. The trial is carried out in consultation with the World Health Organization, the International Society of Hypertension, the European Society of Hypertension and the World Hypertension League. Syst-Eur is a multicentre trial designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality. Secondary endpoints include cardiovascular events, such as myocardial infarction and congestive heart failure. To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized to active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/day), combined with enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), as necessary. The patients of the control group receive matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per-protocol comparison of the outcome in the 2 treatment groups.

Study Overview

• Status: Terminated
• Conditions: Isolated Systolic Hypertension
• Intervention / Treatment: Drug: Active treatment with nitrendipine (10-40 mg/day).

• Study Type: Interventional
• Enrollment (Actual): 4695
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• At least 60 years old.
• Sitting systolic blood pressure on masked placebo, during run-in phase of 160 to 219 mmHg, with a sitting diastolic blood pressure below 95 mmHg and a standing systolic blood pressure of at least 140 mmHg
• Informed consent must be obtained

Exclusion Criteria:

• Systolic hypertension is secondary to a disorder that needed specific medical or surgical treatment.
• Retinal haemorrhage or papilloedema;
• Congestive heart failure
• Dissecting aortic aneurysm
• Serum creatinine concentration at presentation of 180µmol/L or more.
• History of severe nose bleeds.
• Stroke or myocardial infarction in the year before the study.
• Dementia.
• Substance abuse.
• Any disorder prohibiting a sitting or standing position.
• Any severe concomitant cardiovascular or non-cardiovascular disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active treatment; Active treatment with nitrendipine (10-40 mg/day). If necessary, the dihydropyridine calcium-channel blocker was combined with or replaced by enalapril maleate (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both drugs.	Drug: Active treatment with nitrendipine (10-40 mg/day).; If necessary, the dihydropyridine calcium-channel blocker was combined with or replaced by enalapril maleate (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both drugs.
Placebo Comparator: Placebo; Placebo tablets were identical to the study drugs with a similar schedule.	Drug: Active treatment with nitrendipine (10-40 mg/day).; If necessary, the dihydropyridine calcium-channel blocker was combined with or replaced by enalapril maleate (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both drugs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of stroke	Available in Lancet 1997; 350:757-764	3-monthly visits up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	Available in Lancet 1997; 350:757-764	3-monthly visits up to 5 years
Myocardial infarction	Available in Lancet 1997; 350:757-764	3-monthly visits up to 5 years
Congestive heart failure	Available in Lancet 1997; 350:757-764	3-monthly visits up to 5 years

Collaborators and Investigators

• Sponsor: KU Leuven
• Investigators: Principal Investigator: Jan A Staessen, MD, PhD, University of Leuven

Publications and helpful links

General Publications

• Hara A, Thijs L, Asayama K, Jacobs L, Wang JG, Staessen JA. Randomised double-blind comparison of placebo and active drugs for effects on risks associated with blood pressure variability in the Systolic Hypertension in Europe trial. PLoS One. 2014 Aug 4;9(8):e103169. doi: 10.1371/journal.pone.0103169. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: February 1, 1990
• Primary Completion (Actual): February 1, 1997
• Study Completion (Actual): February 1, 1997

Study Registration Dates

• First Submitted: March 10, 2014
• First Submitted That Met QC Criteria: March 13, 2014
• First Posted (Estimate): March 17, 2014

Study Record Updates

• Last Update Posted (Actual): May 11, 2017
• Last Update Submitted That Met QC Criteria: May 10, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Elderly; Stroke; Clinical trial; Cardiovascular complications; Isolated systolic hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Heart Murmurs; Hypertension; Systolic Murmurs; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Nitrendipine
• Other Study ID Numbers: Syst-Eur

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Syst-Eur data are available on request by other investigators, whose research is ethically approved.