Clinical Trials Register

Summary
EudraCT Number:	2020-001014-37
Sponsor's Protocol Code Number:	ALTUM
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-10-21
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-001014-37

A.3

Full title of the trial

Pharmacogenetics of hypertension: randomized monocentric study in patients with essential hypertension and treated with Spironolactone or Torasemide

Farmacogenetica dell’ipertensione: studio monocentrico randomizzato in pazienti affetti da ipertensione essenziale e trattati con Spironolattone o Torasemide

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Pharmacogenetics of hypertension: study with Spironolactone or Torasemide

Farmacogenetica dell’ipertensione: studio con Spironolattone o Torasemide

A.3.2

Name or abbreviated title of the trial where available

Pharmacogenetics of hypertension: study with Spironolactone or Torasemide

Farmacogenetica dell’ipertensione: studio con Spironolattone o Torasemide

A.4.1

Sponsor's protocol code number

ALTUM

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	OSPEDALE SAN RAFFAELE
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	RICERCA FINALIZZATA 2016 Ministero della Salute
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS Ospedale San Raffaele
B.5.2	Functional name of contact point	Ambulatorio Ipertensione - Nefrolog
B.5.3	Address:
B.5.3.1	Street Address	Via Olgettina, 60
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.3.4	Country	Italy
B.5.4	Telephone number	0226432876
B.5.5	Fax number	0226432384
B.5.6	E-mail	lanzani.chiara@hsr.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Torasemide
D.3.2	Product code	[Torasemide]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TORASEMIDE
D.3.9.1	CAS number	56211-40-6
D.3.9.2	Current sponsor code	Torasemide
D.3.9.3	Other descriptive name	Torsemide
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Spironolattone
D.3.2	Product code	[Spironolattone]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SPIRONOLATTONE
D.3.9.1	CAS number	52-01-7
D.3.9.2	Current sponsor code	Spironolattone
D.3.9.3	Other descriptive name	Spironolactone - Aldactone - Spirolactone
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Essential hypertension

Ipertensione essenziale

E.1.1.1

Medical condition in easily understood language

High arterial blood pressure

Pressione arteriosa alta

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	22.1
E.1.2	Level	LLT
E.1.2	Classification code	10015489
E.1.2	Term	Essential hypertension, benign
E.1.2	System Organ Class	10047065 - Vascular disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10015488
E.1.2	Term	Essential hypertension
E.1.2	System Organ Class	10047065 - Vascular disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the difference in the reduction of systolic blood pressure (SBP) values between carriers and non-carriers of the different genotypic combinations for LSS and UMOD in response to Spironolactone or Torasemide after 4 weeks of treatment (T4 vs. T0)

Valutare la differenza nella riduzione dei valori pressori sistolici (deltaPAS) tra i pazienti portatori e non portatori delle diverse combinazioni genotipiche per LSS e UMOD in risposta a Spironolattone o Torasemide dopo 4 settimane di trattamento (T4 vs T0).

E.2.2

Secondary objectives of the trial

a. to evaluate the difference in the reduction of diastolic blood pressure (DBP) values after 4 weeks of treatment in the different genotypic groups (T4 vs. T0).
b. to measure the changes in aldosterone and endogenous ouabain levels in the different genotypic groups after 4 weeks of treatment (T4 vs T0).

a. valutare la differenza nella riduzione dei valori pressori diastolici (deltaPAD) dopo 4 settimane di trattamento nei diversi gruppi genotipici (T4 vs T0).
b. misurare la variazione di aldosterone e dei livelli di ouabaina endogena nei diversi gruppi genotipici dopo 4 settimane di trattamento (T4 vs T0).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

a. male patients aged 25-65 years and female patients aged 45-65 years in menopause
b. naïve hypertensive patients (newly diagnosed, never previously treated) or in therapy with a single anti-hypertensive drug
c. documented hypertension of grade I or II (according to ESH 2013 guidelines, in the untreated patient or despite the therapy).

a. pazienti di sesso maschile di età compresa tra 25-65 anni e pazienti di sesso femminile di età compresa tra 45-65 anni in menopausa
b. pazienti ipertesi naïve (di nuova diagnosi, mai trattati in precedenza) o in terapia con singolo farmaco anti-ipertensivo
c. documentata ipertensione arteriosa grado I o II (secondo linee guida ESH 2013, nel paziente non trattato o nonostante la terapia)

E.4

Principal exclusion criteria

a. known causes of secondary hypertension
b. stage II hypertension (SBP = 180 and DBP = 110 mmHg;
c. history of renal artery stenosis
d. significant kidney disease (eGFR-CK-EPI less than 60 ml/min)
e. refractory hypokalaemia or hyponatraemia (plasma Na < 126 mEq/L)
f. hyperkalaemia (plasma K > 5.5 mEq/L)
g. hypercalcaemia
h. symptomatic hyperuricemia
i. liver disease (transaminases greater than 3 times the maximum laboratory value)
j. cardiac pathologies (previous myocardial infarction, ongoing atrial fibrillation, etc.)
k. diabetes (fasting blood sugar > 126mg/dL)
l. treatment with statins in progress
m. obesity (BMI > 30 kg/m2)
n. known hypersensitivity to the study drugs (Spironolactone or Torasemide) or to any of the excipients

a. cause note di ipertensione secondaria
b. ipertensione stadio II (PAS>= 180 e PAD>=110 mmHg
c. storia di stenosi dell'arteria renale
d. malattia renale significativa (eGFR-CK-EPI inferiore a 60 ml/min)
e. ipokaliemia o iponatriemia refrattarie (Na pl < 126 mEq/l)
f. iperpotassiemia (Kpl > 5.5 mEq/l)
g. ipercalcemia
h. iperuricemia sintomatica
i. malattia epatica (transaminasi superiori a 3 volte il valore massimo del laboratorio)
j. patologie cardiache (infarto miocardico pregresso, fibrillazione atriale in atto, ecc)
k. diabete (glicemia a digiuno >126mg/dL)
l. trattamento con statine in corso
m. obesità (BMI >30 kg/m2)
n. ipersensibilità nota verso i farmaci in studio (Spironolattone o Torasemide) o a uno qualsiasi degli eccipienti

E.5 End points

E.5.1

Primary end point(s)

Changes in systolic blood pressure after treatment with one of the two drugs

Variazioni della pressione arteriosa sistolica dopo trattamento con uno dei due farmaci

E.5.1.1

Timepoint(s) of evaluation of this end point

1 month

1 mese

E.5.2

Secondary end point(s)

Changes in diastolic blood pressure, plasma aldosterone and ouabain values after treatment with one of the two drugs

Variazioni della pressione arteriosa diastolica, dei valori plasmatici di aldosterone e di ouabaina dopo trattamento con uno dei due farmaci

E.5.2.1

Timepoint(s) of evaluation of this end point

1 month

1 mese

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

assetto genetico specifico o non specifico per quel farmaco

genotype-specific or no specif drug responses

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

144

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

144

F.4.2

For a multinational trial

F.4.2.1

In the EEA

144

F.4.2.2

In the whole clinical trial

144

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

At the end of the trial, each hypertensive patient will receive a therapy according to the current guidelines

Al termine della sperimentazione a ciascun paziente iperteso verrà assegnata una terapia secondo linee guida

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-08-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-10

P. End of Trial
P.	End of Trial Status	Ongoing

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