Pharmacogenetics of Torasemide and Spironolactone in Hypertension Treatment

NCT06413082 | Completed Phase 3 DMC

• 1 other identifier: ALTUM
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

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

Conditions

Hypertension; Genetic Predisposition; Drug Effect

Keywords

hypertension; genetics; torasemide; spironolactone; pharmacogenetics

Outcome Measures

Primary Outcomes (1)

• difference in the change of systolic blood pressure(deltaSBP)

  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

  week 4 vs. week 0

Secondary Outcomes (2)

• difference in diastolic blood pressure change after treatment with Spironolactone or difference in diastolic blood pressure reduction (deltaDBP)

  week 4 vs. week 0

• variation of plasma aldosterone

  week 4 vs. week 0

Study Arms (2)

Torasemide

EXPERIMENTAL

The study involves the administration of Torasemide 2.5 mg.

Drug: Torasemide

Spironolactone

EXPERIMENTAL

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

Drug: Spironolactone

Interventions

Torasemide 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

Also known as: Demadex, Tortas, Wator, Torsemide

Torasemide

Spironolactone 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

Also known as: Aldactone, Carospir

Spironolactone

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ospedale San Raffaele: lead

Study Sites (2)

San Raffaele Hospital

Milan, Lombardy, 20132, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

MeSH Terms

Conditions

Hypertension; Genetic Predisposition to Disease

Interventions

Torsemide; Spironolactone; Canrenoic Acid

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienes

Study Officials

• Paolo Manunta, MD

  San Raffaele Hospital Milan, Italy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: medical doctor in nephrology unit, nephrologist

Model Details: single-center, nationwide, randomized, phase III prospective interventional outpatient study, in two arms, in parallel groups

Study Record Dates

• First Submitted: September 4, 2023
• First Posted: May 14, 2024
• Study Start: February 15, 2021
• Primary Completion: July 7, 2023
• Study Completion: September 3, 2023
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)