Pharmacogenetics of Torasemide and Spironolactone in Hypertension Treatment

NCT ID: NCT06413082

Last Updated: 2024-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-15
• Study Completion Date: 2023-09-03

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

Conditions

Hypertension; Genetic Predisposition; Drug Effect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Torasemide

The study involves the administration of Torasemide 2.5 mg.

Group Type: EXPERIMENTAL

Torasemide

Intervention Type: DRUG

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

Spironolactone

The study involves the administration of Spironolactone 50 mg orally every day.

Group Type: EXPERIMENTAL

Spironolactone

Intervention Type: DRUG

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

Interventions

Torasemide

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

Intervention Type: DRUG

Spironolactone

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

Intervention Type: DRUG

Other Intervention Names

Demadex; Tortas; Wator; Torsemide; Aldactone; Carospir

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ospedale San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Chiara Lanzani

medical doctor in nephrology unit, nephrologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paolo Manunta, MD

Role: STUDY_DIRECTOR

San Raffaele Hospital Milan, Italy

Locations

San Raffaele Hospital

Milan, Lombardy, Italy

IRCCS Ospedale San Raffaele

Milan, , Italy

Countries

Italy

Other Identifiers

ALTUM

Identifier Type: -

Identifier Source: org_study_id