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

NCT02499822 | Completed Phase 4

• 1 other identifier: 09F401
• Study Type: interventional
• Target: 168
• Locations: 3 countries
• Sites: 3

Brief Summary

The purpose of this study is

1. 1.to compare the effects of nifedipine GITS and ramipril on blood pressure variability in subjects with elevated blood pressure variability.
2. 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.

Conditions

Hypertension; High Blood Pressure Variability

Keywords

Hypertension; Blood pressure variability; Home systolic blood pressure; Organ damage; Nifedipine GITS; Ramipril

Outcome Measures

Primary Outcomes (1)

• Variability (standard deviation) of home systolic blood pressure at final visit

  After 10 weeks of study treatment

Secondary Outcomes (13)

• 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

• Short term 24h variability of diastolic 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

Study Arms (2)

Nifedipine GITS 30 mg slow release

EXPERIMENTAL

Nifedipine GITS 30 mg slow release in tablets.

Drug: Nifedipine GITS

Ramipril 10 mg

EXPERIMENTAL

Ramipril 10 mg in tablets.

Drug: Ramipril

Interventions

Nifedipine GITS DRUG

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

Nifedipine GITS 30 mg slow release

Ramipril 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

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead
• Bayer: collaborator

Study Sites (3)

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

Shanghai, China

Location

Hypertension Center, Third University Department of Medicine, Sotiria Hospital

Athens, Greece

Location

Istituto Auxologico Italiano

Milan, Italy

Location

Related Publications (11)

• Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F; Task Force Members. 2013 ESH/ESC 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. 2013 Jul;31(7):1281-357. doi: 10.1097/01.hjh.0000431740.32696.cc. No abstract available.

  PMID: 23817082 BACKGROUND

• Parati G, Ochoa JE, Lombardi C, Bilo G. Assessment and management of blood-pressure variability. Nat Rev Cardiol. 2013 Mar;10(3):143-55. doi: 10.1038/nrcardio.2013.1. Epub 2013 Feb 12.

  PMID: 23399972 BACKGROUND

• Liu JG, Xu LP, Chu ZX, Miao CY, Su DF. Contribution of blood pressure variability to the effect of nitrendipine on end-organ damage in spontaneously hypertensive rats. J Hypertens. 2003 Oct;21(10):1961-7. doi: 10.1097/00004872-200310000-00025.

  PMID: 14508204 BACKGROUND

• Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010 Mar 13;375(9718):895-905. doi: 10.1016/S0140-6736(10)60308-X.

  PMID: 20226988 BACKGROUND

• Webb AJ, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. Lancet. 2010 Mar 13;375(9718):906-15. doi: 10.1016/S0140-6736(10)60235-8.

  PMID: 20226989 BACKGROUND

• Ushigome E, Fukui M, Hamaguchi M, Tanaka T, Atsuta H, Ohnishi M, Oda Y, Yamazaki M, Hasegawa G, Nakamura N. Beneficial effect of calcium channel blockers on home blood pressure variability in the morning in patients with type 2 diabetes. J Diabetes Investig. 2013 Jul 8;4(4):399-404. doi: 10.1111/jdi.12052. Epub 2013 Mar 4.

  PMID: 24843686 BACKGROUND

• Wang JG, Yan P, Jeffers BW. Effects of amlodipine and other classes of antihypertensive drugs on long-term blood pressure variability: evidence from randomized controlled trials. J Am Soc Hypertens. 2014 May;8(5):340-9. doi: 10.1016/j.jash.2014.02.004. Epub 2014 Feb 15.

  PMID: 24685006 BACKGROUND

• Levi-Marpillat N, Macquin-Mavier I, Tropeano AI, Parati G, Maison P. Antihypertensive drug classes have different effects on short-term blood pressure variability in essential hypertension. Hypertens Res. 2014 Jun;37(6):585-90. doi: 10.1038/hr.2014.33. Epub 2014 Mar 27.

  PMID: 24671016 BACKGROUND

• Mancia G, Facchetti R, Parati G, Zanchetti A. Visit-to-visit blood pressure variability in the European Lacidipine Study on Atherosclerosis: methodological aspects and effects of antihypertensive treatment. J Hypertens. 2012 Jun;30(6):1241-51. doi: 10.1097/HJH.0b013e32835339ac.

  PMID: 22499291 BACKGROUND

• Matsui Y, O'Rourke MF, Hoshide S, Ishikawa J, Shimada K, Kario K. Combined effect of angiotensin II receptor blocker and either a calcium channel blocker or diuretic on day-by-day variability of home blood pressure: the Japan Combined Treatment With Olmesartan and a Calcium-Channel Blocker Versus Olmesartan and Diuretics Randomized Efficacy Study. Hypertension. 2012 Jun;59(6):1132-8. doi: 10.1161/HYPERTENSIONAHA.111.189217. Epub 2012 Apr 30.

  PMID: 22547439 BACKGROUND

• Zhang W, Liu CY, Bilo G, Soranna D, Zambon A, Kyriakoulis KG, Kollias A, Ceravolo I, Cassago S, Pengo MF, Destounis A, Stergiou GS, Wang JG, Parati G. A Randomized Controlled Trial on the Efficacy and Safety of a Calcium-Channel Blocker and an Angiotensin-Converting Enzyme Inhibitor in Chinese and European Patients with Hypertension. Am J Hypertens. 2025 Mar 17;38(4):248-256. doi: 10.1093/ajh/hpae152.

  PMID: 39657776 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Ramipril

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Gianfranco Parati, MD

  Istituto Auxologico Italiano - Milan, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2015
• First Posted: July 16, 2015
• Study Start: October 1, 2015
• Primary Completion: July 3, 2020
• Study Completion: November 1, 2020
• Last Updated: September 30, 2021

Record last verified: 2021-09

Locations

GR (1); CN (1); IT (1)