Clinical trial NCT00415038: Efficacy of Rostafuroxin in the Treatment of Essential Hypertension
Official title: A Double Blind, Dose Range, Placebo Controlled Study of the Effects of Rostafuroxin vs Placebo in Patients With Stable, Uncomplicated, Essential Hypertension.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Hypertension
Keywords: hypertension
pharmacogenomic
adducin
ouabain
rostafuroxin
Lead sponsor: sigma-tau i.f.r. S.p.A.
Sponsor class: INDUSTRY
First posted: 2006-12-22
Enrollment: 438
Sex: ALL
Minimum age (years): 30
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Office Systolic Blood Pressure after 5 week of treatment
timeFrame: 5 weeks
Secondary outcomes:
measure: Office Diastolic Blood Pressure
timeFrame: 5 weeks
measure: Proportion of normalised and responder patients (all visits)
timeFrame: 5 weeks
measure: 24 hours BP monitoring (through to peak ratio)
timeFrame: 5 weeks
measure: Effect on sub-populations, genetically selected
timeFrame: 5 weeks
measure: safety of the drug
timeFrame: monitored during all the study
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Catholic University of Leuven - Laboratory of Hypertension, Dept. of Molecular and Cardiov. Research - Campus Gasthuisberg
Study officials:
affiliation: Catholic University of Leuven, Laboratory of Hypertension Dept. of Molecular and cardiovascular Resesrach - Campus Gasthuisberg
name: Jan A Staessen, MD PhD
role: STUDY_CHAIR
affiliation: Catholic University of Leuven Dept. of Molecular and cardiovascular Research, Laboratory of Hypertension
name: Hilde Celis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jagiellonian University Medical College Krakow - I Cardiac Department - Krakow (Poland)
name: Kalina Kawecka-Jaszcz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Hypertension and Diabetology - Medical Academy - Gdansk (Poland)
name: Bogdan Wyrzykowski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of hypertension - School of Medicine - Poznan (Poland)
name: Andrzej Tykarski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Postgraduate Medical School - Department of cardiology - Warszawa (Poland)
name: Miroslaw Dluzniewski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal Medicine and Hypertension Warszawa (Poland)
name: Andrzey Januszewicz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal Medicine and Gerontology - Jagiellonian University Medical College - Krakow (Poland)
name: Tomasz Grodzicki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Coronary Disease Department - Jagiellonian University medical College - Krakow (Poland)
name: Wieslawa Piwowarska, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IV Clinica Medica dell'Università di Padova, Dipartimento di Medicina Clinica e Sperimentale - Padova (Italy)
name: Edoardo Casiglia, MD
role: STUDY_DIRECTOR
affiliation: U.O. Cardiologia - Ospedale Civile di Schio (Vicenza) Italy
name: Giancarlo Basso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Divisione di Nefrologia, Dialisi e Ipertensione - Ospedale S. Raffaele - Milano (Italy)
name: Paolo Manunta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro per L'ipertensione A.S.L. n° 1 - Sassari (Italy)
name: Nicola Glorioso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dipartimento di Medicina Interna, Nefrologia e dialisi - Ospedale San Giovanni Battista - Foligno (Perugia) Italy
name: Gianni Bellomo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unità di valutazione dell'efficacia clinica - Direzione Aziendale Ospedale S. Maria delle Croci - Ravenna (Italy)
name: Ezio Degli Esposti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of internal Medicine, Siberian Branch of the Russian Academy of Medical Sciences - Novosibirsk (Russia)
name: Yuri Nikitin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal Medicine, Postgraduate Education Faculty Smolensk State medical Academy - Smolensk (Russia)
name: Viktor Milyagin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal and family Medicine - Volgograd (Russia)
name: Sergey Nedogoda, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Portiuncola Hospital Cardiac Research Department - Ballinasloe co Galway (Ireland)
name: James Barton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Ziekenhuis Maastricht Afdeling Nefrologie - Mastricht (The Netherlands)
name: Peter W De Leeuw, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Medicine/Nephrology Maaslandziekenhuis - Sittard (The Netherlands)
name: Marielle ME Krekels, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical center, Hypertension Department - Ljubljana (Slovenia)
name: Rock Accetto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de la Salud de Vistalegre - La Flota, Murcia (Spain)
name: Fernando Hernandez-Menarguez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Salud Murcias San Andres - Murcia (Spain)
name: Jose a Aleman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinico Universitario - Santiago de Compostela (Spain)
name: Carlos c Gomez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Conxo - Santiago de Compostela (Spain)
name: Antonio Pose-Reino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Sagunto - Sagunto (Valencia) - Spain
name: Jose M Pascual-Izuel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hipertension Clinic, Hospital Clinico University of Valencia - Valencia (Spain)
name: Josep Redon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinico de Barcelona - Barcelona (Spain)
name: Antonio Coca-Payeras, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Derpartment of Internal Medicine 2, Faculty of Medicine - Pilsen (Czech Republic)
name: Jan Filipovsky, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal Medicine 2, St. Anne's Hospital, Faculty of Medicine - Brno (Czech Republic)
name: Miroslav Soucek, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Division de Nephrologie, Department de Medecine, Centre Hopitalier Universitaire Vaudois - Lausanne (Switzerland)
name: Michel Burnier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.