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

NCT00408512 | Completed Phase 4

• 1 other identifier: FARM5STRH9 AIFA
• Study Type: interventional
• Target: 2,500
• Locations: 1 country
• Sites: 1

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

Conditions

Essential Hypertension

Keywords

treatment; adverse events; adherence; gene; polymorphism

Outcome Measures

Primary Outcomes (3)

• Persistance and adherence to treatment

  2 years

• changes in markers of preclinical cardiovascular disease

  2 years

• Changes in global cardiovascular risk based on the ESH/ESC table of risk

  2 years

Secondary Outcomes (1)

• genetic mechanism of adverse events in response to treatment with thyazides

  20 years

Study Arms (2)

Thiazides

ACTIVE COMPARATOR

Thiazidic diuretic

Drug: thiazides

Non Tiazidic

ACTIVE COMPARATOR

Non tiazidic diuretic treatment: Any other therapy can be considered in this arm: example: CCB, BB, ACEi, ARB

Procedure: Non thiazidic treatment

Interventions

thiazides DRUG

Up to 25 mg per day

Thiazides

Non thiazidic treatment PROCEDURE

Amximum tolerated dosage as indicated from the label

Non Tiazidic

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Federico II University: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (1)

Ambulatorio Ipertensione e Unità Coronarica Federico II University

Napoli, 80131, Italy

Location

Related Publications (3)

• Nishizaka MK, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003 Nov;16(11 Pt 1):925-30. doi: 10.1016/s0895-7061(03)01032-x.

  PMID: 14573330 BACKGROUND

• Chittani M, Zaninello R, Lanzani C, Frau F, Ortu MF, Salvi E, Fresu G, Citterio L, Braga D, Piras DA, Carpini SD, Velayutham D, Simonini M, Argiolas G, Pozzoli S, Troffa C, Glorioso V, Kontula KK, Hiltunen TP, Donner KM, Turner ST, Boerwinkle E, Chapman AB, Padmanabhan S, Dominiczak AF, Melander O, Johnson JA, Cooper-Dehoff RM, Gong Y, Rivera NV, Condorelli G, Trimarco B, Manunta P, Cusi D, Glorioso N, Barlassina C. TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives. J Hypertens. 2015 Jun;33(6):1301-9. doi: 10.1097/HJH.0000000000000541.

  PMID: 25695618 DERIVED

• Trimarco V, Izzo R, Migliore T, Rozza F, Marino M, Manzi MV, De Marco M, de Simone G, De Luca N. Should thiazide diuretics be given as first line antihypertensive therapy or in addition to other medications? High Blood Press Cardiovasc Prev. 2015 Mar;22(1):55-9. doi: 10.1007/s40292-014-0065-0. Epub 2014 Jun 24.

  PMID: 24956971 DERIVED

Related Links

• website of the High Blood Pressure Outpatient Clinic and UTIC of "Federico II" University of Naples

MeSH Terms

Conditions

Essential Hypertension

Interventions

Thiazides

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfur Compounds; Organic Chemicals

Study Officials

• Bruno Trimarco, MD

  Federico II University, Dipartimento di medicina Clinica Scienze Cardiovascoalri ed Immunologiche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 6, 2006
• First Posted: December 7, 2006
• Study Start: December 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: March 1, 2010
• Last Updated: June 27, 2011

Record last verified: 2009-11

Locations

IT (1)