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

Phase 4

Completed

• Conditions: High Blood Pressure Variability; Hypertension
• Interventions: Drug: Nifedipine GITS; Drug: Ramipril

• Registration Number: NCT02499822
• Lead Sponsor: Istituto Auxologico Italiano

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.

Study Timeline

• Study First Submitted: 2015-07-10
• Study First Submitted QC: 2015-07-14
• Study First Posted: 2015-07-16
• Study Start: 2015-10
• Primary Completion: 2020-07-03
• Study Completion: 2020-11-01
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-29
• Last Update Posted: 2021-09-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 168

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nifedipine GITS 30 mg slow release	Nifedipine GITS	Nifedipine GITS 30 mg slow release in tablets.
Ramipril 10 mg	Ramipril	Ramipril 10 mg in tablets.

Primary Outcome Measures

Name	Time	Method
Variability (standard deviation) of home systolic blood pressure at final visit	After 10 weeks of study treatment

Secondary Outcome Measures

Name	Time	Method
Short term 24h variability of diastolic blood pressure at final visit (24h weighted standard deviation)	At baseline and after 10 weeks of study treatment
Variability (standard deviation) of home diastolic blood pressure measured at final visit	At baseline and after 10 weeks of study treatment
Short term 24h variability of systolic blood pressure at final visit (24h weighted standard deviation)	At baseline and after 10 weeks of study treatment
Visit-to-visit variability (standard deviation) of systolic blood pressure assessed over the three last visits	At baseline and after 6, 8 and 10 weeks of study treatment
Visit-to-visit variability (standard deviation) of diastolic blood pressure assessed over the three last visits	At baseline and after 6, 8 and 10 weeks of study treatment
Mean 24 hour systolic blood pressure at final visit	At baseline and after 10 weeks of study treatment
Mean 24 hour diastolic blood pressure at final visit	At baseline and after 10 weeks of study treatment
Sokolow index at the end of the extension study	At baseline and after 12 months of study treatment
Cornell voltage duration index at the end of the extension study	At baseline and after 12 months of study treatment
Left ventricular mass index at the end of the extension study	At baseline and after 12 months of study treatment
Microalbuminuria (albumin-creatinine ratio) at the end of the extension study	At baseline and after 12 months of study treatment
Carotid-femoral pulse wave velocity (cfPWV) at the end of the extension study	At baseline and after 12 months of study treatment
Estimated glomerular filtration rate (eGFR, by CKD-EPI formula) at the end of the extension study	At baseline and after 12 months of study treatment

Trial Locations

Locations (3)

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