Pharmacosurveillance and Pharmacogenetics of First-line Diuretics in Hypertension: The StayOnDiur Study
Status:
Completed
Trial end date:
2010-03-01
Target enrollment:
Participant gender:
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