Drug Effect, Genetic Predisposition, Hypertension
Conditions
Keywords
hypertension, genetics, torasemide, spironolactone, pharmacogenetics
Brief summary
Phase III interventional study to evaluate the different efficacy of Torasemide and Spironolactone in reducing systolic blood pressure in carriers and non-carriers of the different genotypic combinations for Lanosterol and Uromodulin
Detailed description
The investigators will enroll 144 naïve hypertensive subjects who will undertake 2-4 weeks of run-in and 4 weeks of treatment (7 day window at each visit). During this period partecipants will follow a low sodium diet (about 5g/day) and will be monitored with blood chemistry tests
Interventions
DRUGTorasemide
The assignment to each drug will be carried out randomly in each genotypic group with the aim of reaching the same number of patients treated with the two drugs in the different genotypic groups
DRUGSpironolactone
The assignment to each drug will be carried out randomly in each genotypic group with the aim of reaching the same number of patients treated with the two drugs in the different genotypic groups
Sponsors
Ospedale San Raffaele
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The study will be double-blind with respect to the genetic analysis and open-label with an observer blind with respect to the primary endpoint.
Intervention model description
single-center, nationwide, randomized, phase III prospective interventional outpatient study, in two arms, in parallel groups
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* male (25-65 years) and female (45-65 years in menopause defined as 12 consecutive months of amenorrhea for which no other physiological or pathological cause has been identified in woman over 45 years of age) * newly diagnosed hypertensive patients never treated before or on single antihypertensive drug therapy * hypertension grade I or II (according to 2013 ESH guidelines, in the patient untreated or despite therapy), defined as the following: * at visits T-4 and T-2 (week -4 and week -2 ± 7 days, run-in period) the mean of the last 3 consecutive SBP measurements must be \>=140 mmHg and/or diastolic BP\>= 90mmHg * at the T0 visit (week 0 ± 7 days, enrollment), the mean of the last 3 consecutive systolic BP measurements must be \>=140 mmHg and \<180 mmHg and diastolic BP must be \>=90 mmHg and \<110 mmHg * signing of the informed consent for participation in the study and for genotyping.
Exclusion criteria
* known causes of secondary hypertension * stage II hypertension (SBP\>= 180 and SBP\>=110 mmHg * history of renal artery stenosis * significant kidney disease (eGFR-CK-EPI less than 60 mL/min) * refractory hypokalemia or hyponatremia (Napl \< 126 mEq/L) * hyperkalemia (K \> 5.5 mEq/l) * hypercalcemia * symptomatic hyperuricemia * liver disease (transaminases greater than 3 times the maximum laboratory value) * cardiac pathologies (previous myocardial infarction, atrial fibrillation in progress, etc.) * diabetes (fasting blood sugar \>126mg/dL) -. current statin treatment * obesity (BMI \>30 kg/m2) * ongoing pregnancy * breastfeeding in progress * anuria * hypovolemia and dehydration * known hypersensitivity to the study drugs (Spironolactone or Torasemide) or to any of the excipients * ongoing therapy with aminoglycosides or cephalosporins * participation in a clinical study in which an investigational drug was administered within 30 days or 5 half-lives prior to the study drug * patients unable to express valid consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| difference in the change of systolic blood pressure(deltaSBP) | week 4 vs. week 0 | the difference in the reduction of systolic blood pressure (deltaSBP) values in essential hypertensive patients who are carriers and noncarriers of the different genotypic combinations for the LSS (lanosterol synthase) and UMOD (uromodulin) genes in response to Spironolactone or Torasemide |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| difference in diastolic blood pressure change after treatment with Spironolactone or difference in diastolic blood pressure reduction (deltaDBP) | week 4 vs. week 0 | the difference in the reduction of diastolic blood pressure (deltaDBP) values in essential hypertensive patients who are carriers and noncarriers of the different genotypic combinations for the LSS (lanosterol synthase) and UMOD (uromodulin) genes in response to Spironolactone or Torasemide |
| variation of plasma aldosterone | week 4 vs. week 0 | variation of plasma aldosterone levels in the different genotypic and treatment groups after 4 weeks of treatment. |
Countries
Italy
Outcome results
None listed