Pharmacogenetics of Torasemide and Spironolactone in Hypertension Treatment

Hypertension Clinical Trial

— ALTUM  

Official title:

Pharmacogenetics of Hypertension: a Single-centre Randomized Study in Patients With Essential Hypertension Treated With Spironolactone or Torasemide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06413082
• Other study ID #: ALTUM
• Status: Completed
• Phase: Phase 3
• Start date: February 15, 2021
• Est. completion date: September 3, 2023

Study information

• Verified date: May 2024
• Source: Ospedale San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: September 3, 2023
• Est. primary completion date: July 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Effect
• Genetic Predisposition
• Genetic Predisposition to Disease
• Hypertension

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
Italy	IRCCS Ospedale San Raffaele	Milan
Italy	San Raffaele Hospital	Milan	Lombardia

Sponsors (1)

Lead Sponsor	Collaborator
Ospedale San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	difference in diastolic blood pressure change after treatment with Spironolactone or difference in diastolic blood pressure reduction (deltaDBP)	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	week 4 vs. week 0
Secondary	variation of plasma aldosterone	variation of plasma aldosterone levels in the different genotypic and treatment groups after 4 weeks of treatment.	week 4 vs. week 0