Pharmacogenetics of Torasemide and Spironolactone in Hypertension Treatment

Phase 3

Completed

• Conditions: Hypertension; Genetic Predisposition; Drug Effect
• Interventions: Drug: Torasemide; Drug: Spironolactone

• Registration Number: NCT06413082
• Lead Sponsor: Ospedale San Raffaele

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

Study Timeline

• Study Start: 2021-02-15
• Primary Completion: 2023-07-07
• Study Completion: 2023-09-03
• Study First Submitted: 2023-09-04
• Status Verified: 2024-05
• Study First Submitted QC: 2024-05-11
• Study First Posted: 2024-05-14
• Last Update Submitted: 2024-05-14
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Torasemide	Torasemide	The study involves the administration of Torasemide 2.5 mg.
Spironolactone	Spironolactone	The study involves the administration of Spironolactone 50 mg orally every day.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (2)

San Raffaele Hospital; 🇮🇹 Milan, Lombardia, Italy

IRCCS Ospedale San Raffaele; 🇮🇹 Milan, Italy