Clinical trial NCT06413082: Pharmacogenetics of Torasemide and Spironolactone in Hypertension Treatment
Official title: Pharmacogenetics of Hypertension: a Single-centre Randomized Study in Patients With Essential Hypertension Treated With Spironolactone or Torasemide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Genetic Predisposition
Drug Effect
Keywords: hypertension
genetics
torasemide
spironolactone
pharmacogenetics
Lead sponsor: Ospedale San Raffaele
Sponsor class: OTHER
First posted: 2024-05-14
Enrollment: 38
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single-center, nationwide, randomized, phase III prospective interventional outpatient study, in two arms, in parallel groups
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: difference in the change of systolic blood pressure(deltaSBP)
timeFrame: week 4 vs. week 0
Secondary outcomes:
measure: difference in diastolic blood pressure change after treatment with Spironolactone or difference in diastolic blood pressure reduction (deltaDBP)
timeFrame: week 4 vs. week 0
measure: variation of plasma aldosterone
timeFrame: week 4 vs. week 0
Other outcomes:
Locations:
city: Milan
country: Italy
facility: San Raffaele Hospital
state: Lombardia
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
Study officials:
affiliation: San Raffaele Hospital Milan, Italy
name: Paolo Manunta, MD
role: STUDY_DIRECTOR
References: