REducing Blood Pressure Variability in Essential Hypertension With RAmipril vErsus Nifedipine GITS Trial

NCT ID: NCT02499822

Last Updated: 2021-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2020-11-01

Brief Summary

The purpose of this study is

1. to compare the effects of nifedipine GITS and ramipril on blood pressure variability in subjects with elevated blood pressure variability.

2. to assess whether the degree of treatment-induced changes in blood pressure variability, is related to the degree of regression (or progression) of organ damage in heart, kidneys and carotid arteries.

Detailed Description

Elevated blood pressure variability (BPV) is associated with adverse cardiovascular outcomes and organ damage in hypertensive subjects. An antihypertensive treatment able to reduce BPV independently of BP lowering effect might thus provide additional protection in terms of cardiovascular risk in subjects with elevated BPV, independently on its effect of BP itself. However, data on the effects of different classes of antihypertensive drugs on BPV are limited and inconsistent. Some studies have suggested a possible usefulness of calcium antagonists in this setting. Based on the above considerations the investigators hypothesize that a calcium channel blocker nifedipine GITS, will provide a greater BPV lowering effect, when compared with ramipril, independently from the reduction in mean BP level. Based on the above considerations, the primary objective of this study is to compare the effects of nifedipine GITS and ramipril on different estimates of BPV (24 h BPV, home BPV, and visit-to-visit BPV) in subjects with elevated BPV. The secondary objective is to assess whether the degree of treatment-induced changes in BPV, is related to the degree of regression (or progression) of organ damage, after accounting for mean BP reduction by treatment.

Conditions

Hypertension; High Blood Pressure Variability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Nifedipine GITS 30 mg slow release

Nifedipine GITS 30 mg slow release in tablets.

Group Type: EXPERIMENTAL

Nifedipine GITS

Intervention Type: DRUG

Commercially available drug formulations are used. Study medication will be assumed in a single morning (7-10 a.m.) administration per os.

Ramipril 10 mg

Ramipril 10 mg in tablets.

Group Type: EXPERIMENTAL

Ramipril

Intervention Type: DRUG

Commercially available drug formulations are used. Study medication will be assumed in a single morning (7-10 a.m.) administration per os.

Interventions

Nifedipine GITS

Commercially available drug formulations are used. Study medication will be assumed in a single morning (7-10 a.m.) administration per os.

Intervention Type: DRUG

Ramipril

Commercially available drug formulations are used. Study medication will be assumed in a single morning (7-10 a.m.) administration per os.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female subjects
• Age 35-75 years
• Clinic systolic BP ≥140 mmHg and/or diastolic BP ≥ 90 mmHg (under no antihypertensive treatment)
• Daytime BP on ambulatory BP monitoring (ABPM) ≥135 mmHg systolic and/or ≥85 mmHg diastolic (under no antihypertensive treatment)
• Home SBP standard deviation (SD) >7 mmHg and/or daytime ambulatory SBP SD >12 mmHg
• Patients may be included if untreated or, if treated with one antihypertensive drug or two drugs in low doses, after 2 weeks' washout period
• Written informed consent to participate in the study

Exclusion Criteria

• Subjects treated with ≥ 2 antihypertensive drugs (except those on two drugs in low doses)
• Treated subjects with on-treatment clinic BP ≥160 mmHg systolic and/or 100 mmHg diastolic
• Treated antihypertensive subjects in whom withdrawal of treatment is deemed unethical by the investigator (e.g. because of the existence of compelling indications other than hypertension for continuous use of previously used antihypertensive agent)
• Contraindications to study treatments as detailed in the relative Summaries of Medical Product Characteristics for ramipril (hypersensitivity to ramipril or any of the excipients or any other ACE inhibitor, history of angioneurotic oedema, extracorporeal treatments leading to contact of blood with negatively charged surfaces, significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney, second and third trimesters of pregnancy, lactation, haemodynamically relevant renal artery stenosis, hypotensive or haemodynamically unstable patients) or nifedipine GITS (known hypersensitivity to nifedipine or to any of the excipients, pregnancy before week 20 and during breastfeeding, cardiovascular shock, concomitant treatment with rifampicin, patients with a Kock pouch)
• Cardiovascular diseases other than hypertension (coronary heart disease, heart failure or left ventricular systolic dysfunction of any degree, atrial fibrillation or frequent arrhythmias, valvular or congenital heart disease, cardiomyopathies, cerebrovascular disease, peripheral artery disease, aortic aneurysm)
• Chronic kidney disease
• Suspected or confirmed secondary hypertension
• Diabetes mellitus
• Subjects with conditions other than those mentioned above, where compelling indications for the use of any specific class of antihypertensive medication exist, according to current (e.g. European Society of Cardiology) guidelines
• Other conditions deemed relevant by the investigator (including respiratory disorders, liver disease, renal disease, thyroid disorders)
• BMI ≥35 kg/m2
• Known severe obstructive sleep apnea (apnea-hypopnea index > 30 or use of CPAP)
• Premenopausal women not using effective contraceptive methods
• Elevated probability of noncompliance with the study procedures

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Istituto Auxologico Italiano

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gianfranco Parati, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Auxologico Italiano - Milan, Italy

Locations

Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital Shanghai Institute of Hypertension, Shanghai Jiaotong University School of Medicine

Shanghai, , China

Hypertension Center, Third University Department of Medicine, Sotiria Hospital

Athens, , Greece

Istituto Auxologico Italiano

Milan, , Italy

Countries

China; Greece; Italy

References

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Other Identifiers

09F401

Identifier Type: -

Identifier Source: org_study_id