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Pharmacosurveillance and Pharmacogenetics of First-line Diuretics in Hypertension: The StayOnDiur Study (stayondiur)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00408512
Recruitment Status : Completed
First Posted : December 7, 2006
Last Update Posted : June 27, 2011
Agenzia Italiana del Farmaco
Information provided by:
Federico II University

Brief Summary:

Background: The use of thiazide diuretics in the treatment of hypertension (HT) is widely considered a first line treatment, given the efficacy and low cost of this class of drugs. This indication is not unanimous, because thiazides can cause metabolic alterations and other side effects increasing cardiac and cerebrovascular risk, which reduce compliance to treatment and increase health care system cost. However, large intervention trials in HT suggest that the improvement in cardiovascular prognosis of HT patients depends more on follow-up procedures than on type of drug used. Furthermore, the investigators have documented improved compliance to antihypertensive therapy by implementing cooperation between general practitioners (GPs) and HT specialists.

Objectives: In a multicenter, open label randomized study the investigators will compare the persistence on therapy of thiazides versus other treatments, as a first line antihypertensive therapy, in a clinical setting characterized by a strict cooperation between GPs and HT specialist. The investigators will also analyse candidate genes with impact on drug-induced metabolic alterations to elucidate the pathophysiology of these phenomena.

Methods: 260 GPs will recruit 2600 hypertensive patients with indication to pharmacological treatment and randomise them to starting treatment with chlortalidone (12.5 to 25 mg daily, 1300 pts) or a GP decided single drug (excluding thiazides) or combination therapy at highest tolerated dose. In both groups any other class of antihypertensive drugs can be added over time in order to achieve blood pressure control (<140/90 mmHg). Follow-up will last 2 years. Blood sample and urine analyses, carotid and cardiac ultrasound will be performed at baseline and scheduled time points. Genotyping will be performed by sequencing. Data will be collected and stored using a web based centralized Case Report Form (CRF) Expected results: Results will highlight whether a follow-up strategy based on tight cooperation between GPs and HT specialists can allow the use of thiazides as first line antihypertensive therapy without any negative effect on persistence, adherence and efficacy of the treatment. These data can be used to reduce total burden of the Health Care System in HT by replacing more expensive drugs with diuretics in the 50% of hypertensive patients, who do not receive this class of drugs. Furthermore, the pharmacogenetic approach may clarify the pathophysiological mechanisms of drug-induced metabolic side effects

Condition or disease Intervention/treatment Phase
Essential Hypertension Drug: thiazides Procedure: Non thiazidic treatment Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Increasing Stay-on-therapy in Hypertensive Patients Treated With First-line Diuretics: An Active Pharmacosurveillance and Pharmacogenetic Study.
Study Start Date : December 2006
Actual Primary Completion Date : December 2009
Actual Study Completion Date : March 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Thiazides
Thiazidic diuretic
Drug: thiazides
Up to 25 mg per day

Active Comparator: Non Tiazidic
Non tiazidic diuretic treatment: Any other therapy can be considered in this arm: example: CCB, BB, ACEi, ARB
Procedure: Non thiazidic treatment
Amximum tolerated dosage as indicated from the label

Primary Outcome Measures :
  1. Persistance and adherence to treatment [ Time Frame: 2 years ]
  2. changes in markers of preclinical cardiovascular disease [ Time Frame: 2 years ]
  3. Changes in global cardiovascular risk based on the ESH/ESC table of risk [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. genetic mechanism of adverse events in response to treatment with thyazides [ Time Frame: 20 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Hypertensive patients will be 18 to 75-year old.
  • Eligible patients will be asked for written informed consent and thereafter referred to the identified Hypertension Specialist Centre located in their areas, for end-organ damage evaluation by echocardiography, carotid ultrasound and urine dip-stick.
  • Eligible patients are required to have stage Ic or II essential hypertension, and to be previously untreated or poorly controlled. They will be selected by GPs participating into the study. Similar to untreated patients, those with poor control of blood pressure under multiple-drug therapy will start treatment with one single drug, which will be titrated to the highest dose before adding subsequent medications, based on the GP's judgement.
  • Hypertension will be defined according to 2003 ESH/ESC guidelines (1). Blood and urine tests will be performed, according to guidelines for Hypertension Management For General Practitioners (GP) of the Regione Campania (see BURC number 11, 18/02/2002). This screening includes cell blood counts (CBCs), serum creatinine, sodium, potassium, uric acid, total cholesterol, triglycerides, HDL-cholesterol, glucose, urine analysis and EKG. LDL will be calculated starting from the total cholesterol, triglyceride and HDL-cholesterol.

Exclusion Criteria:

  • Omen in fertile age not using recognized contraceptive methods, or pregnant or nursing will be excluded from the protocol, since the use of many antihypertensive drugs is contraindicated in pregnancy and lactation.
  • Patients will be excluded when presenting with documented coronary or cerebrovascular events in the previous 6 months, NYHA class higher than 1
  • History of congestive heart failure
  • Secondary hypertension
  • Cancer disease
  • Renal disease (serum creatinine >2 mg/dl)
  • Liver cirrhosis or severe dysfunction, or any other health problem that may interfere with the projected 2 year follow-up.

Data will be stored in an electronic database located in the Coordinating Centre, to which GPs may have access for uploading data on a daily base, using personal, encrypted, login and password. These data will be stored in the central database. After local echocardiographic evaluation, patients showing left ventricular Ejection Fraction < 45% will be excluded from the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00408512

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Ambulatorio Ipertensione e Unità Coronarica Federico II University
Napoli, Italy, 80131
Sponsors and Collaborators
Federico II University
Agenzia Italiana del Farmaco
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Study Director: Bruno Trimarco, MD Federico II University, Dipartimento di medicina Clinica Scienze Cardiovascoalri ed Immunologiche
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Bruno Trimarco, Federico II University Identifier: NCT00408512    
Other Study ID Numbers: FARM5STRH9 AIFA
First Posted: December 7, 2006    Key Record Dates
Last Update Posted: June 27, 2011
Last Verified: November 2009
Keywords provided by Federico II University:
adverse events
Additional relevant MeSH terms:
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Essential Hypertension
Vascular Diseases
Cardiovascular Diseases