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Pharmacogenomics of Hypertension Personalized Medicine (PGX-HT)

Phase 3
Conditions
Hypertension
Interventions
Drug: Peri
Registration Number
NCT03249285
Lead Sponsor
Ospedale San Raffaele
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

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
300
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:

    1. 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);
    2. 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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Peri no profilePeripatient with no genetic profile, receiving after randomisation Perindopril treatment with 4-8 mg/day oral for 4-8 weeks
HCTZ no profileHCTZpatient with no genetic profile, receiving after randomisation HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks
Peri profile yesPeripatient with genetic Perindopril profile, receiving Perindopril treatment with 4-8 mg/day oral for 4-8 weeks
HCTZ profile yesHCTZpatient with genetic HCTZ profile, receiving HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks
Primary Outcome Measures
NameTimeMethod
SBP (Systolic blood pressure) and DBP (Diastolic blood pressure) response4 and 8 weeks

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

Secondary Outcome Measures
NameTimeMethod
Profiles implementationin the three months after the end of the study

Implementing and redefining the genetic profile for HCTZ or/and Peri by using a further spectrum of 128 different SNP variants

Trial Locations

Locations (3)

Azienda Sanitaria 6

🇮🇹

Livorno, Italy

Azienda Ospedaliero - Universitaria S. Maria della Misericordia

🇮🇹

Udine, Italy

San Raffaele Hospital

🇮🇹

Milan, Italy

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