Efficacy of Rostafuroxin in the Treatment of Essential Hypertension

A Double Blind, Dose Range, Placebo Controlled Study of the Effects of Rostafuroxin vs Placebo in Patients With Stable, Uncomplicated, Essential Hypertension.

The purpose of this study is to verify the efficacy of Rostafuroxin in the treatment of essential hypertension and to determine the best effective dose to be administered in the general hypertensive population and in a subset of this population in which genetic patterns could be involved in the etiology of essential hypertension.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: Rostafuroxin; Drug: Rostafuroxin; Drug: Rostafuroxin; Drug: Rostafuroxin; Drug: Rostafuroxin

Detailed Description

Elevated arterial pressure is probably the most important public health problem. about 30% of the world adult population are affected by hypertension in industrialised countries. Development of a pharmacogenomic approach to the therapy of primary hypertension give new opportunities for the treatment of hypertension. This approach consists in the identification of the genetic-molecular mechanisms responsible for hypertension in a given subset of patients, and in the development of drugs able to interfere with such mechanisms, thus leading to very selective therapeutic interventions with enhanced efficacy and reduced side effects.

• Study Type: Interventional
• Enrollment (Actual): 438
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • Catholic University of Leuven - Laboratory of Hypertension, Dept. of Molecular and Cardiov. Research - Campus Gasthuisberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with grade 1 or 2 of essential hypertension
• Less than 3 risk factors (age > 55 if male, smoking, dyslipidemia, family history of CV disease occurring before 55 years in men and 65 in women
• Naive patients or currently on monotherapy or one combination tablet
• SBP between 140 and 169 mmHg

Exclusion Criteria:

• Atrial fibrillation or left or right VBBB
• Left ventricular hypertrophy
• Significant renal or hepatic disease
• Obesity > 30kg/m2
• Diabetes mellitus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rostafuroxin 50 micrograms capsules; 5 weeks, once a day capsule treatment of active drug or placebo, followed by a 5 weeks, once a day capsule treatment of placebo or active drug according to a cross-over design	Drug: Rostafuroxin; 1 capusle of 50 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 150 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 500 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 1.5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin
Experimental: Rostafuroxin 150 micrograms capsules; 5 weeks, once a day capsule treatment of active drug or placebo, followed by a 5 weeks, once a day capsule treatment of placebo or active drug according to a cross-over design	Drug: Rostafuroxin; 1 capusle of 50 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 150 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 500 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 1.5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin
Experimental: Rostafuroxin 500 micrograms capsules; 5 weeks, once a day capsule treatment of active drug or placebo, followed by a 5 weeks, once a day capsule treatment of placebo or active drug according to a cross-over design	Drug: Rostafuroxin; 1 capusle of 50 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 150 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 500 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 1.5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin
Experimental: Rostafuroxin 1.5 mg capsules; 5 weeks, once a day capsule treatment of active drug or placebo, followed by a 5 weeks, once a day capsule treatment of placebo or active drug according to a cross-over design	Drug: Rostafuroxin; 1 capusle of 50 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 150 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 500 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 1.5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin
Experimental: Rostafuroxin 5 mg capsule; 5 weeks, once a day capsule treatment of active drug or placebo, followed by a 5 weeks, once a day capsule treatment of placebo or active drug according to a cross-over design	Drug: Rostafuroxin; 1 capusle of 50 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 150 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 500 micrograms of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 1.5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin; Drug: Rostafuroxin; 1 capusle of 5 milligrams of Rostafuroxin or placebo per day in the morning before breakfast for 5 weeks followed by other 5 weeks with placebo or Rostafuroxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Office Systolic Blood Pressure after 5 week of treatment	5 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Office Diastolic Blood Pressure	5 weeks
Proportion of normalised and responder patients (all visits)	5 weeks
24 hours BP monitoring (through to peak ratio)	5 weeks
Effect on sub-populations, genetically selected	5 weeks
safety of the drug	monitored during all the study

Collaborators and Investigators

• Sponsor: sigma-tau i.f.r. S.p.A.
• Investigators: Study Chair: Jan A Staessen, MD PhD, Catholic University of Leuven, Laboratory of Hypertension Dept. of Molecular and cardiovascular Resesrach - Campus Gasthuisberg; Principal Investigator: Hilde Celis, MD, Catholic University of Leuven Dept. of Molecular and cardiovascular Research, Laboratory of Hypertension; Principal Investigator: Kalina Kawecka-Jaszcz, MD, Jagiellonian University Medical College Krakow - I Cardiac Department - Krakow (Poland); Principal Investigator: Bogdan Wyrzykowski, MD, Department of Hypertension and Diabetology - Medical Academy - Gdansk (Poland); Principal Investigator: Andrzej Tykarski, MD, Department of hypertension - School of Medicine - Poznan (Poland); Principal Investigator: Miroslaw Dluzniewski, MD, Postgraduate Medical School - Department of cardiology - Warszawa (Poland); Principal Investigator: Andrzey Januszewicz, MD, Department of Internal Medicine and Hypertension Warszawa (Poland); Principal Investigator: Tomasz Grodzicki, MD, Department of Internal Medicine and Gerontology - Jagiellonian University Medical College - Krakow (Poland); Principal Investigator: Wieslawa Piwowarska, MD, Coronary Disease Department - Jagiellonian University medical College - Krakow (Poland); Study Director: Edoardo Casiglia, MD, IV Clinica Medica dell'Università di Padova, Dipartimento di Medicina Clinica e Sperimentale - Padova (Italy); Principal Investigator: Giancarlo Basso, MD, U.O. Cardiologia - Ospedale Civile di Schio (Vicenza) Italy; Principal Investigator: Paolo Manunta, MD, Divisione di Nefrologia, Dialisi e Ipertensione - Ospedale S. Raffaele - Milano (Italy); Principal Investigator: Nicola Glorioso, MD, Centro per L'ipertensione A.S.L. n° 1 - Sassari (Italy); Principal Investigator: Gianni Bellomo, MD, Dipartimento di Medicina Interna, Nefrologia e dialisi - Ospedale San Giovanni Battista - Foligno (Perugia) Italy; Principal Investigator: Ezio Degli Esposti, MD, Unità di valutazione dell'efficacia clinica - Direzione Aziendale Ospedale S. Maria delle Croci - Ravenna (Italy); Principal Investigator: Yuri Nikitin, MD, Institute of internal Medicine, Siberian Branch of the Russian Academy of Medical Sciences - Novosibirsk (Russia); Principal Investigator: Viktor Milyagin, MD, Department of Internal Medicine, Postgraduate Education Faculty Smolensk State medical Academy - Smolensk (Russia); Principal Investigator: Sergey Nedogoda, MD, Department of Internal and family Medicine - Volgograd (Russia); Principal Investigator: James Barton, MD, Portiuncola Hospital Cardiac Research Department - Ballinasloe co Galway (Ireland); Principal Investigator: Peter W De Leeuw, MD, Academisch Ziekenhuis Maastricht Afdeling Nefrologie - Mastricht (The Netherlands); Principal Investigator: Marielle ME Krekels, MD, Department of Medicine/Nephrology Maaslandziekenhuis - Sittard (The Netherlands); Principal Investigator: Rock Accetto, MD, University Medical center, Hypertension Department - Ljubljana (Slovenia); Principal Investigator: Fernando Hernandez-Menarguez, MD, Centro de la Salud de Vistalegre - La Flota, Murcia (Spain); Principal Investigator: Jose a Aleman, MD, Centro de Salud Murcias San Andres - Murcia (Spain); Principal Investigator: Carlos c Gomez, MD, Hospital Clinico Universitario - Santiago de Compostela (Spain); Principal Investigator: Antonio Pose-Reino, MD, Hospital de Conxo - Santiago de Compostela (Spain); Principal Investigator: Jose M Pascual-Izuel, MD, Hospital de Sagunto - Sagunto (Valencia) - Spain; Principal Investigator: Josep Redon, MD, Hipertension Clinic, Hospital Clinico University of Valencia - Valencia (Spain); Principal Investigator: Antonio Coca-Payeras, MD, Hospital Clinico de Barcelona - Barcelona (Spain); Principal Investigator: Jan Filipovsky, MD, Derpartment of Internal Medicine 2, Faculty of Medicine - Pilsen (Czech Republic); Principal Investigator: Miroslav Soucek, MD, Department of Internal Medicine 2, St. Anne's Hospital, Faculty of Medicine - Brno (Czech Republic); Principal Investigator: Michel Burnier, MD, Division de Nephrologie, Department de Medecine, Centre Hopitalier Universitaire Vaudois - Lausanne (Switzerland)

Publications and helpful links

General Publications

• Staessen JA, Kuznetsova T, Acceto R, Bacchieri A, Brand E, Burnier M, Celis H, Citterio L, de Leeuw PW, Filipovsky J, Fournier A, Kawecka-Jaszcz K, Manunta P, Nikitin Y, O'Brien ET, Redon J, Thijs L, Ferrari P, Valentini G, Bianchi G. OASIS-HT: design of a pharmacogenomic dose-finding study. Pharmacogenomics. 2005 Oct;6(7):755-75. doi: 10.2217/14622416.6.7.755.
• Staessen JA, Thijs L, Stolarz-Skrzypek K, Bacchieri A, Barton J, Espositi ED, de Leeuw PW, Dluzniewski M, Glorioso N, Januszewicz A, Manunta P, Milyagin V, Nikitin Y, Soucek M, Lanzani C, Citterio L, Timio M, Tykarski A, Ferrari P, Valentini G, Kawecka-Jaszcz K, Bianchi G. Main results of the ouabain and adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin. Trials. 2011 Jan 14;12:13. doi: 10.1186/1745-6215-12-13.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): April 1, 2007
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: December 21, 2006
• First Submitted That Met QC Criteria: December 21, 2006
• First Posted (Estimate): December 22, 2006

Study Record Updates

• Last Update Posted (Estimate): June 17, 2011
• Last Update Submitted That Met QC Criteria: June 16, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: hypertension; pharmacogenomic; ouabain; adducin; rostafuroxin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: PST2238-DM-03-010