Pharmacogenomics of Hypertension Personalized Medicine (PGX-HT)

San Donato Group (GSD)

Status and phase: Unknown; Phase 3

Conditions: Hypertension

Treatments: Drug: Peri; Drug: HCTZ

Study type: Interventional

Funder types: Other

Identifiers

NCT03249285

udraCT NUMBER: 2015-001888-39

Details and patient eligibility

About

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.

Full 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

Enrollment: 300 estimated patients

Sex: All

Ages: 25 to 60 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 4 patient groups

Peri profile yes

Experimental group

Description:

patient with genetic Perindopril profile, receiving Perindopril treatment with 4-8 mg/day oral for 4-8 weeks

Treatment:

Drug: Peri

HCTZ profile yes

Experimental group

Description:

patient with genetic HCTZ profile, receiving HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks

Treatment:

Drug: HCTZ

Peri no profile

Active Comparator group

Description:

patient with no genetic profile, receiving after randomisation Perindopril treatment with 4-8 mg/day oral for 4-8 weeks

Treatment:

Drug: Peri

HCTZ no profile

Active Comparator group

Description:

patient with no genetic profile, receiving after randomisation HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks

Treatment:

Drug: HCTZ