Clinical Trials Register

Summary
EudraCT Number:	2020-000973-26
Sponsor's Protocol Code Number:	SOGALDI-PEF
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-02-02
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Portugal - INFARMED

A.2

EudraCT number

2020-000973-26

A.3

Full title of the trial

SOdium-Glucose cotransporter 2 inhibitor, ALDosterone AntagonIst, or both for heart failure with Preserved Ejection Fraction: a two-centre randomised three-treatment three-period crossover trial

Inibidor do co-transportador de sódio e glucose 2, antagonista da aldosterona ou ambos para o tratamento da Insuficiência Cardíaca com Fração de Ejeção Preservada: Ensaio clínico aleatorizado cruzado de 3 tratamentos por 3 períodos, em 2 centros

A.3.1

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

SOdium-Glucose cotransporter 2 inhibitor, ALDosterone AntagonIst, or both for heart failure with Preserved Ejection Fraction: a two-centre randomised three-treatment three-period crossover trial

A.3.2

Name or abbreviated title of the trial where available

Not applicable

A.4.1

Sponsor's protocol code number

SOGALDI-PEF

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	Faculdade de Medicina da Universidade do Porto
B.1.3.4	Country	Portugal
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	Faculdade de Medicina da Universidade do Porto
B.4.2	Country	Portugal
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	BlueClinical – Investigação e Desenvolvimento em Saúde, Lda
B.5.2	Functional name of contact point	BlueClinical, Lda.
B.5.3	Address:
B.5.3.1	Street Address	Avenida Villagarcia de Arosa, 1919 – 1º
B.5.3.2	Town/ city	Matosinhos
B.5.3.3	Post code	4460-439
B.5.3.4	Country	Portugal
B.5.4	Telephone number	+351220 995 159
B.5.5	Fax number	+351223 200 699
B.5.6	E-mail	regulatory@blueclinical.pt

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.2.1.1.1	Trade name	Forxiga 10 mg comprimidos revestidos por película
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Not applicable
D.3.2	Product code	Not applicable
D.3.4	Pharmaceutical form	Film-coated 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	Dapagliflozin
D.3.9.1	CAS number	461432-26-8
D.3.9.4	EV Substance Code	SUB31650
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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.2.1.1.1	Trade name	Aldactone 25 mg comprimidos
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratórios Pfizer, Lda.
D.2.1.2	Country which granted the Marketing Authorisation	Portugal
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	Not applicable
D.3.2	Product code	Not applicable
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	Spironolactone
D.3.9.3	Other descriptive name	Spironolactone
D.3.9.4	EV Substance Code	SUB10631MIG
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

Heart Failure with Preserved Ejection Fraction

E.1.1.1

Medical condition in easily understood language

Heart Failure with Preserved Ejection Fraction

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10076396
E.1.2	Term	Heart failure with preserved ejection fraction
E.1.2	System Organ Class	100000004849

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 assess the effect of the spironolactone-dapagliflozin combination vs. spironolactone alone on the percentage change of the circulating levels of log-transformed NT-pro BNP relative to the baseline log NT-pro BNP levels.

E.2.2

Secondary objectives of the trial

- To assess the effect of the spironolactone-dapagliflozin combination vs. dapagliflozin alone on the percentage change of the circulating levels of log-transformed NT-pro BNP relative to the baseline log NT-pro BNP level.
- To assess the effect of the spironolactone-dapagliflozin combination vs. spironolactone and dapagliflozin alone periods on the proportion of patients reaching 20% or greater reduction in NT-pro BNP levels
- To compare the change in left atrial volume and blood pressure between the spironolactone-dapagliflozin combination period vs. spironolactone and dapagliflozin alone periods
- To compare the change in quality-of-life score
- To compare the effect of spironolactone, dapagliflozin, and spironolactone-dapagliflozin combination on the change of exercise tolerance, endothelial function, vascular structure, systemic congestion, natriuresis, glycosuria and microalbuminuria.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of informed consent prior to any study specific procedures
2. HFpEF diagnosis (irrespective of time from diagnosis)
3. Male or female patients, aged ≥50 years
4. NYHA Class II-IV
5. LVEF ≥45%
6. NT-pro BNP ≥220 pg/mL or BNP ≥80 pg/mL if in sinus rhythm (SR)
7. NT-pro BNP ≥660 pg/mL or BNP ≥240 pg/mL if in atrial fibrillation (AF)
8. Echocardiography with at least one of the following criteria:
a. LAVI ≥29 ml/m2 (≥34 ml/m2 if AF)
b. Lateral E/e` ≥9
c. LVMI ≥115 g/m2 If male or ≥95 g/m2 if female
d. LV wall thickness ≥12mm
9. eGFR ≥30 ml/min/1.73m2 (CKD-EPI formula)
10. Blood Potassium ≤5.5 mmol/L
11. Not treated with MRAs and/or SGLT2i within the previous month before inclusion and have no history of diabetic ketoacidosis while in treatment with SGLT2 inhibitors
12. Stable/chronic ambulatory patients i.e., patients without need for hospitalization within the last 30 days due to heart failure decompensation episodes
13. If female, she must be a woman of non-childbearing potential. That is, she must be:
a. Surgically sterilized (e.g. underwent hysterectomy, bilateral salpingectomy or
bilateral oophorectomy)
b. Clinically diagnosed infertile
c. In a post-menopausal state, defined as no menses for 12 months without an
alternative medical cause.
14. A female patient of childbearing potential must have a negative serum pregnancy test
at Visit 1 (Day 0) and must agree to consistently and correctly use (from 28 days prior to first study treatment administration until at least 7 days after last study treatment administration) one of the following highly effective methods of contraception:
a. Abstinence of heterosexual intercourse (when this is in line with preferred and usual lifestyle of the subject)
b. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
c. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
d. Intrauterine device
e. Intrauterine hormone-releasing system
f. Bilateral tubal occlusion
g. Vasectomized partner, who has received medical assessment of the surgical success, or clinically diagnosed infertile partner

E.4

Principal exclusion criteria

1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
2. Participation in another clinical study with an investigational product during the last month
3. Unwilling or unable to sign the informed consent form
4. Surgical procedure, coronary, cerebral or peripheral vascular events or sepsis in the prior 90 days
5. Cancer (life-limiting or less than 2 years in remission)
6. Any previously confirmed autoimmune disease
7. Type 1 Diabetes
8. Severe hepatic impairment (Child-Pugh class C)
9. Ability to walk is, in the investigator’s opinion, clearly limited by joint disease or other locomotor problems or lung diseases rather than by cardiorespiratory fitness
10. Previously confirmed cardiac amyloidosis
11. Severe valvulopathy according to the echocardiogram report
12. Patients with a known hypersensitivity or intolerance to spironolactone or dapagliflozin or any of the excipients of the products.
13. Female patients currently pregnant (confirmed by a positive pregnancy test) or intent to become pregnant or breast feeding.

E.5 End points

E.5.1

Primary end point(s)

Log-transformed NT-pro BNP

E.5.1.1

Timepoint(s) of evaluation of this end point

During the entire study

E.5.2

Secondary end point(s)

• Log-transformed NT-pro BNP
• LAVi
• Blood pressure
• KCCQ score
• Visual analogic symptom scale
• VO2max
• Pulse-wave velocity
• Peripheral arterial tonometry (PAT) and reactive hyperaemia index
• Pulmonary congestion evaluated by lung ultrasonography;
• Bioelectrical impedance analysis
• Glucose (urine)
• Urinary sodium/natriuresis (urine);
• Microalbuminuria (urine);

E.5.2.1

Timepoint(s) of evaluation of this end point

During the entire study

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

E.6.4

Safety

Yes

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

108

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)

None. Not applicable

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

2022-06-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-03-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-11-29

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials