Clinical Trials Register

Summary
EudraCT Number:	2022-002266-33
Sponsor's Protocol Code Number:	SATURN
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-07-11
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

Spain - AEMPS

A.2

EudraCT number

2022-002266-33

A.3

Full title of the trial

STATINS USE IN INTRACEREBRAL HEMORRHAGE PATIENTS (SATURN)

USO DE ESTATINAS EN PACIENTES CON HEMORRAGIA INTRACEREBRAL

A.3.1

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

STATINS USE IN INTRACEREBRAL HEMORRHAGE PATIENTS (SATURN)

USO DE ESTATINAS EN PACIENTES CON HEMORRAGIA INTRACEREBRAL

A.4.1

Sponsor's protocol code number

SATURN

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03936361

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	BETH ISRAEL DEACONESS MEDICAL CENTER
B.1.3.4	Country	United States
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	NIH/NINDS
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Institut de Recerca H. Santa Creu i Sant Pau
B.5.2	Functional name of contact point	Neurology Department
B.5.3	Address:
B.5.3.1	Street Address	Sant Quinti 89
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08041
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34935537099
B.5.6	E-mail	jmarti@santpau.cat

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	Simvastatina
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Simvastatina
D.3.4	Pharmaceutical form	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	Simvastatin
D.3.9.1	CAS number	79902-63-9
D.3.9.4	EV Substance Code	SUB10529MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 80
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	Atorvastatina
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Atorvastatina
D.3.4	Pharmaceutical form	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	Atorvastatin
D.3.9.1	CAS number	134523-00-5
D.3.9.4	EV Substance Code	SUB05600MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	10 to 80
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

Intracerebral Hemorrhage (ICH) recurrence

Recurrencia de hemorragia intracerebral (HIC)

E.1.1.1

Medical condition in easily understood language

Intracerebral Hemorrhage (ICH) recurrence

Recurrencia de hemorragia intracerebral (HIC)

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

EFFICACY - To determine the effects of continuation vs. discontinuation of statins on the risk of ICH recurrence during 24 months of follow-up in patients presenting with a spontaneous lobar lCH while taking a statin drug. Specifically, we wish to determine the effects of discontinuing vs. continuing statins on the risk of recurrent symptomatic ICH. We hypothesize that discontinuation of statins in patients with lobar ICH is likely associated with reduced risk of ICH recurrence.

SAFETY - To determine the effects of continuation vs. discontinuation of statins on the occurrence of any of the following MACCE (symptomatic ischemic stroke, symptomatic myocardial infarction, newly symptomatic arterial occlusive disease (peripheral, retinal, or carotid), revascularization procedures for coronary, carotid, or peripheral arterial disease, and vascular death).

EFICACIA - Determinar los efectos de la continuación frente a la interrupción de las estatinas sobre el riesgo de recurrencia de la HIC durante 24 meses de seguimiento en pacientes que presentan una HIC lobar espontánea mientras toman una estatina. Específicamente, deseamos determinar los efectos de discontinuar versus continuar con las estatinas sobre el riesgo de HIC sintomática recurrente. Presumimos que la interrupción de las estatinas en pacientes con HIC lobular probablemente se asocie con un riesgo reducido de recurrencia de la HIC.

SEGURIDAD - Determinar los efectos de la continuación frente a la interrupción de las estatinas sobre la aparición de cualquiera de los siguientes MACCE (accidente cerebrovascular isquémico sintomático, infarto de miocardio sintomático, enfermedad oclusiva arterial sintomática reciente (periférica, retiniana o carotídea), procedimientos de revascularización para cirugía coronaria, carotídea, o enfermedad arterial periférica, y muerte vascular).

E.2.2

Secondary objectives of the trial

1. To examine quality of life, functional, and cognitive outcomes in patients in whom statins are continued vs. discontinued, by repeated assessments of the EQ-5D quality of life questionnaire, modified Rankin Scale (mRS), and Telephone Montreal Cognitive Assessment (T-MoCA) at 3, 6, 9, 12, 18, and 24 months. We hypothesize that patients who discontinue statins will achieve better outcomes than those who continue statins because of reduced risk of ICH recurrence.
2. To prospectively examine whether the presence vs. absence of APOE ε4 and APOE ε2 genotypes modifies the effects of statins on the risk of recurrent ICH (i.e., whether APOE genotype can be used as a biological marker to stratify the risk of ICH recurrence in statins-treated patients).

1. Examinar la calidad de vida, los resultados funcionales y cognitivos en pacientes en quienes se continúa o se interrumpe el tratamiento con estatinas, mediante evaluaciones repetidas del cuestionario de calidad de vida EQ-5D, la escala de Rankin modificada (mRS) y la evaluación cognitiva telefónica de Montreal ( T-MoCA) a los 3, 6, 9, 12, 18 y 24 meses. Nuestra hipótesis es que los pacientes que interrumpen las estatinas lograrán mejores resultados que aquellos que continúan con las estatinas debido a la reducción del riesgo de recurrencia de HIC.
2. Examinar prospectivamente si la presencia frente a la ausencia de los genotipos APOE ε4 y APOE ε2 modifica los efectos de las estatinas sobre el riesgo de HIC recurrente (es decir, si el genotipo APOE puede usarse como marcador biológico para estratificar el riesgo de recurrencia de HIC en pacientes tratados con estatinas).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥ 50 years.
2. Spontaneous lobar ICH confirmed by CT or MRI scan
3. Patient was taking a statin drug at the onset of the qualifying/index ICH
4. Randomization must be carried out within 7 days of the onset of the qualifying ICH
5. Patient or LAR, after consultation with the physicians prescribing statin, agrees to be randomized to statin continuation (restart) vs. discontinuation.

1. Edad ≥ 50 años.
2. HIC lobar espontánea confirmada por tomografía computarizada o resonancia magnética
3. El paciente estaba tomando una estatina al inicio de la HIC clasificatoria/índice
4. La aleatorización debe llevarse a cabo dentro de los 7 días posteriores al inicio de la ICH calificada
5. El paciente o LAR, después de consultar con los médicos que prescriben la estatina, acepta ser aleatorizado para continuar con la estatina (reiniciar) o suspenderla.

E.4

Principal exclusion criteria

1. Suspected secondary cause for the qualifying ICH, such as an underlying vascular abnormality or tumor, trauma, venous infarction, or hemorrhagic transformation of an ischemic infarct.
2. History of recent myocardial infarction (attributed to coronary artery disease) or unstable angina within the previous 3 months
3. Diabetic patients with history of myocardial infarction or coronary revascularization
4. History of familial hypercholesterolemia
5. Patients receiving proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors
6. Known diagnosis of severe dementia
7. Inability to obtain informed consent
8. Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, or other obvious reasons for noncompliance, such as unable to adhere to the protocol specified visits/assessments.
9. Life expectancy of less than 24 months due to co-morbid terminal conditions.
10. Pre-morbid mRS >3
11. ICH score >3 upon presentation.
12. Contraindications to continuation/resumption of statin therapy, such as significant elevations of serum creatinine kinase and/or liver transaminases, and rhabdomyolysis
13. Concurrent participation in another research protocol for investigation of experimental therapy.
14. Women of childbearing potential
15. Indication that withdrawal of care will be implemented for the qualifying ICH.

1. Sospecha de causa secundaria para la ICH calificada, como una anormalidad vascular o tumor subyacente, traumatismo, infarto venoso o transformación hemorrágica de un infarto isquémico.
2. Antecedentes de infarto de miocardio reciente (atribuido a enfermedad arterial coronaria) o angina inestable en los 3 meses anteriores
3. Pacientes diabéticos con antecedentes de infarto de miocardio o revascularización coronaria
4. Historia de hipercolesterolemia familiar
5. Pacientes que reciben inhibidores de la proproteína convertasa subtilisina kexina 9 (PCSK9)
6. Diagnóstico conocido de demencia grave
7. Incapacidad para obtener el consentimiento informado
8. Pacientes de los que se sabe o se sospecha que no pueden cumplir con el protocolo del estudio debido a alcoholismo, dependencia de drogas u otras razones obvias de incumplimiento, como la imposibilidad de cumplir con las visitas/evaluaciones especificadas en el protocolo.
9. Expectativa de vida de menos de 24 meses debido a condiciones terminales comórbidas.
10. mRS premórbido >3
11. Puntuación ICH >3 al momento de la presentación.
12. Contraindicaciones para la continuación/reanudación del tratamiento con estatinas, como elevaciones significativas de la creatinina quinasa sérica y/o transaminasas hepáticas y rabdomiolisis
13. Participación simultánea en otro protocolo de investigación para la investigación de terapia experimental.
14. Mujeres en edad fértil
15. Indicación de que se implementará el retiro de la atención para el ICH calificado.

E.5 End points

E.5.1

Primary end point(s)

EFFICACY - For subjects with an event (recurrent symptomatic ICH), the time to event will be the time from randomization to the event.
SAFETY - The primary safety outcome is the occurrence of MACCE. MACCE will be defined as symptomatic ischemic stroke, symptomatic myocardial infarction, newly symptomatic arterial occlusive disease (peripheral, retinal, or carotid), revascularization procedures for coronary, carotid, or peripheral arterial disease, and vascular death. Ischemic strokes attributed to causes other than atherosclerosis or cardio-embolism, such as arterial dissection, and myocardial infarction (MI) due to causes other than coronary artery disease, such as MI due to hypovolemia or hemodynamic compromise will be recorded separately. A central adjudication committee blinded to treatment allocation will adjudicate all imaging data and all outcome events. The risk/benefit associated with discontinuation of statins will be quantified via longitudinal analyses of EQ-5D and mRS as pre-specified secondary efficacy outcomes.

EFICACIA - Para sujetos con un evento (HIC sintomática recurrente), el tiempo hasta el evento será el tiempo desde la aleatorización hasta el evento.
SEGURIDAD - El principal resultado de seguridad es la aparición de MACCE. MACCE se definirá como accidente cerebrovascular isquémico sintomático, infarto de miocardio sintomático, enfermedad oclusiva arterial sintomática reciente (periférica, retiniana o carotídea), procedimientos de revascularización para enfermedad arterial coronaria, carotídea o periférica y muerte vascular. Los accidentes cerebrovasculares isquémicos atribuidos a causas distintas de la aterosclerosis o la cardioembolia, como la disección arterial, y el infarto de miocardio (IM) debido a causas distintas de la enfermedad arterial coronaria, como el IM debido a hipovolemia o compromiso hemodinámico, se registrarán por separado. Un comité de adjudicación central cegado a la asignación del tratamiento adjudicará todos los datos de imágenes y todos los eventos de resultado. El riesgo/beneficio asociado con la interrupción de las estatinas se cuantificará mediante análisis longitudinales de EQ-5D y mRS como resultados de eficacia secundarios preespecificados.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 months

24 meses

E.5.2

Secondary end point(s)

Quality of life, functional, and cognitive outcomes.
Presence vs. absence of APOE ε4 and APOE ε2 genotypes

Calidad de vida, resultados funcionales y cognitivos.
Presencia vs. ausencia de los genotipos APOE ε4 y APOE ε2

E.5.2.1

Timepoint(s) of evaluation of this end point

At 3, 6, 9, 12, 18, and 24 months

A los 3, 6, 9, 12, 18, y 24 meses

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)

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

Yes

E.8.1.7.1

Other trial design description

PROBE (Prospective Randomized Open, Blinded End-point)

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

Suspensión del tratamiento

Discontinuation of therapy

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

United States

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

Última visita del último sujeto

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

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:

1000

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

456

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

180

F.4.2

For a multinational trial

F.4.2.1

In the EEA

200

F.4.2.2

In the whole clinical trial

1456

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)

The expected normal treatment of the condition in study

El tratamiento según la práctica clínica habitual

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

2022-10-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-09-21

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

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