## Protocol Section
### Identification Module
**NCT ID:** NCT06413082

**Acronym:** ALTUM

**Brief Title:** 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

#### Organization Study ID Info
**ID:** ALTUM
#### Organization
**Class:** OTHER
**Full Name:** Ospedale San Raffaele
### Status Module
#### Completion Date
**Date:** 2023-09-03

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2023-07-07

**Type:** ACTUAL

#### Start Date
**Date:** 2021-02-15

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2023-09-04
**Study First Submit QC Date:** 2024-05-11
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Ospedale San Raffaele

#### Responsible Party

**Investigator Affiliation:** Ospedale San Raffaele

**Investigator Full Name:** Chiara Lanzani

**Investigator Title:** medical doctor in nephrology unit, nephrologist

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**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 Module

**Conditions:**

- Hypertension

- Genetic Predisposition

- Drug Effect

**Keywords:**

- hypertension

- genetics

- torasemide

- spironolactone

- pharmacogenetics

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

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

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** 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.

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 38

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** The study involves the administration of Torasemide 2.5 mg.

**Intervention Names:**

- Drug: Torasemide

**Label:** Torasemide

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Drug: Spironolactone

**Label:** Spironolactone

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Torasemide

**Description:** 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

**Name:** Torasemide

**Other Names:**

- Demadex

- Tortas

- Wator

- Torsemide

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Spironolactone

**Description:** 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

**Name:** Spironolactone

**Other Names:**

- Aldactone

- Carospir

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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

**Measure:** difference in the change of systolic blood pressure(deltaSBP)

**Time Frame:** week 4 vs. week 0

#### Secondary Outcomes

**Description:** 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

**Measure:** difference in diastolic blood pressure change after treatment with Spironolactone or difference in diastolic blood pressure reduction (deltaDBP)

**Time Frame:** week 4 vs. week 0

**Description:** variation of plasma aldosterone levels in the different genotypic and treatment groups after 4 weeks of treatment.

**Measure:** variation of plasma aldosterone

**Time Frame:** week 4 vs. week 0

### Eligibility Module

**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

**Maximum Age:** 65 Years

**Minimum Age:** 25 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Milan

**Country:** Italy

**Facility:** San Raffaele Hospital

**State:** Lombardia

**Zip:** 20132

**Location 2:**

**City:** Milan

**Country:** Italy

**Facility:** IRCCS Ospedale San Raffaele

**Zip:** 20132

#### Overall Officials

**Official 1:**

**Affiliation:** San Raffaele Hospital Milan, Italy

**Name:** Paolo Manunta, MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**Description:** IDP will be stored in the institutional repository.

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000004198

- Term: Disease Susceptibility

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10024

- Name: Hypertension

- Relevance: HIGH

- As Found: Hypertension

- ID: M1470

- Name: Essential Hypertension

- Relevance: LOW

- As Found: Unknown

- ID: M21875

- Name: Genetic Predisposition to Disease

- Relevance: HIGH

- As Found: Genetic Predisposition

- ID: M7380

- Name: Disease Susceptibility

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006973

- Term: Hypertension

- ID: D000020022

- Term: Genetic Predisposition to Disease

### Intervention Browse Module - Ancestors

- ID: D000000451

- Term: Mineralocorticoid Receptor Antagonists

- ID: D000006727

- Term: Hormone Antagonists

- ID: D000006730

- Term: Hormones, Hormone Substitutes, and Hormone Antagonists

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000062865

- Term: Diuretics, Potassium Sparing

- ID: D000004232

- Term: Diuretics

- ID: D000045283

- Term: Natriuretic Agents

- ID: D000000959

- Term: Antihypertensive Agents

- ID: D000049994

- Term: Sodium Potassium Chloride Symporter Inhibitors

- ID: D000049990

- Term: Membrane Transport Modulators

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: AnAg

- Name: Antihypertensive Agents

- Abbrev: NaAg

- Name: Natriuretic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M1912

- Name: Torsemide

- Relevance: HIGH

- As Found: Behavioral counseling

- ID: M15943

- Name: Spironolactone

- Relevance: HIGH

- As Found: Wrist

- ID: M3797

- Name: Mineralocorticoid Receptor Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M11871

- Name: Mineralocorticoids

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M9788

- Name: Hormone Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M7411

- Name: Diuretics

- Relevance: LOW

- As Found: Unknown

- ID: M30025

- Name: Diuretics, Potassium Sparing

- Relevance: LOW

- As Found: Unknown

- ID: M4277

- Name: Antihypertensive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M26153

- Name: Sodium Potassium Chloride Symporter Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077786

- Term: Torsemide

- ID: D000013148

- Term: Spironolactone

### Misc Info Module

- Version Holder: 2024-05-31
