Pharmacogenomics of Hypertension Personalized Medicine (PGX-HT)

Study Overview
=================
Brief Summary
-----------------
This is a pharmacogenomic prospective , four-arms, parallel groups, active comparator controlled study in essential hypertensive patients never treated before. Each patient will be genotyped for SNPs (single nucleotide polymorphism) in preliminary genetic profiles and will be treated according to their genetic profile with Peri (Perindopril) 4 mg or HCTZ ( hydrochlorothiazide) 12.5 mg.

Detailed Description
-----------------
At screening visit each patient will be genotyped for SNPs in preliminary genetic profiles with a custom SNP array. The therapy scheme includes 2-4-week run-in period after which eligible patients will be treated according to their genetic profile with Peri 4 mg or HCTZ 12.5 mg. Titration to Peri 8 mg or HCTZ 25 mg could be possible after one month treatment. Patients without any genetic profile will be randomly assigned to HCTZ or Peri treatment as control groups. The treatment period will last 8 weeks, while the study about 10-12 weeks Four cases may occur: patient with HCTZ profile, HCTZ treatment; patient with Peri profile, Peri treatment; patient without HCTZ nor Peri profile, randomization for HCTZ or Peri; patient with both profiles, treatment according to the profile with the higher number of positive contributors. Eligible patients will be treated according to their genetic profile with Peri 4 mg or HCTZ 12.5 mg/die. Titration to Peri 8 mg or HCTZ 25 mg could be possible after 4 weeks treatment. The treatment period will last 8 weeks, while the study about 10-12 weeks

Official Title
-----------------
Pharmacogenomics Of Hypertension: A New Approach For A Personalized Medicine

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Drug: Peri
* Drug: HCTZ


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male/Female patients aged 25-60 years. Naive hypertensive patients (newly diagnosed, never treated before). Documented mild to moderate arterial hypertension, as defined below: At Visits 1 and 2 (week -4 and week -2 run-in period) the mean of the last 3 consecutive readings of office SBP must be >= 140 mmHg and/or DBP must be >=90 mmHg, when measured by office blood pressure (OBP); At Visit 3 (week 0) enrolment , the mean of the last 3 consecutive readings of SBP must be >= 140 mmHg and <160 mmHg, and DBP must be >= 90 mmHg and <110 mmHg, when measured by OBP. Signed informed consent for genotyping. Exclusion Criteria: known causes of secondary hypertension; pregnant, nursing women or women of childbearing potential taking anti-contraceptive medication; severe or malignant hypertension; history of renal artery disease; significant renal disease (estimated creatinine clearance less than 60 mL/min); hepatic disease; cardiac diseases (myocardial infarction, atrial fibrillation, etc); diabetes (fasting plasma glucose >125mg/dL); statin treatment; obesity (BMI>30 kg/m2).

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peri profile yes<br>patient with genetic Perindopril profile, receiving Perindopril treatment with 4-8 mg/day oral for 4-8 weeks | Drug: Peri<br>* Perindopril 4 mg /day, orally with titration to 8 mg/day after 1 month if BP (Blood pressure) is not controlled<br>* Other names: Perindopril;|
| Experimental: HCTZ profile yes<br>patient with genetic HCTZ profile, receiving HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks | Drug: HCTZ<br>* Hydrochlorothiazide 12, 5 mg day, orally with titration to 25 mg/day after 1 month if BP is not controlled<br>* Other names: Hydrochlorothiazide;|
| Active Comparator: Peri no profile<br>patient with no genetic profile, receiving after randomisation Perindopril treatment with 4-8 mg/day oral for 4-8 weeks | Drug: Peri<br>* Perindopril 4 mg /day, orally with titration to 8 mg/day after 1 month if BP (Blood pressure) is not controlled<br>* Other names: Perindopril;|
| Active Comparator: HCTZ no profile<br>patient with no genetic profile, receiving after randomisation HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks | Drug: HCTZ<br>* Hydrochlorothiazide 12, 5 mg day, orally with titration to 25 mg/day after 1 month if BP is not controlled<br>* Other names: Hydrochlorothiazide;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SBP (Systolic blood pressure) and DBP (Diastolic blood pressure) response | Difference in SBP and DBP variation after 4 and 8 weeks of therapy according to the presence or not of specific genetic profile for each drugs | 4 and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profiles implementation | Implementing and redefining the genetic profile for HCTZ or/and Peri by using a further spectrum of 128 different SNP variants | in the three months after the end of the study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hypertension, pharmacogenomics, anti-hypertensive therapy