Clinical Trials Register

Summary
EudraCT Number:	2021-000938-34
Sponsor's Protocol Code Number:	MYTHS
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-04-04
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2021-000938-34

A.3

Full title of the trial

Single blind randomized controlled trial to assess the safety and efficacy of high dose pulse intravenous corticosteroid therapy to treat patients with complicated/fulminant acute myocarditis

A.3.1

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

Trial to asses the safety and efficacy of of high dose pulse intravenous corticosteroid therapy to treat patients with complicated/fulminant acute myocarditis

A.3.2

Name or abbreviated title of the trial where available

MYTHS trial (MYocarditis THerapy with Steroids) trial

A.4.1

Sponsor's protocol code number

MYTHS

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	Antwerp University Hospital
B.1.3.4	Country	Belgium
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	the Italian Ministry of Health (GR-2019-12368506)
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Antwerp University hospital
B.5.2	Functional name of contact point	Research department cardiology
B.5.3	Address:
B.5.3.1	Street Address	Wilrijkstraat 10
B.5.3.2	Town/ city	Edegem
B.5.3.3	Post code	2650
B.5.3.4	Country	Belgium
B.5.6	E-mail	studiescardiologie@uza.be

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	SoluMedrol- Methylprednisolone
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER S.A. (BELGIUM
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.4	Pharmaceutical form	Powder and solvent for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute (Fulminant) Myocarditis

E.1.1.1

Medical condition in easily understood language

Myocarditis is an inflammatory response within the myocardium with necrosis of cardiac myocyte cells.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

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

The primary objective is to demonstrate a reduction in the rate of the primary composite endpoint on patients treated with pulsed corticosteroid therapy vs. standard therapy and maximal supportive care.

E.2.2

Secondary objectives of the trial

The main secondary objectives are to demonstrate a reduction in the rate of the main secondary composite endpoint on patients treated pulsed corticosteroid therapy vs. standard therapy and maximal supportive care.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients admitted to hospital for suspected AM complicated by acute HF/cardiogenic shock and left ventricular systolic dysfunction will be screened for randomization.
Inclusion criteria are:
*Age 18 years or older and below 70 years (18-69 years)
*Acute HF with clinically suspected acute myocarditis based on an N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration of 1600 pg/mL or more or a B-type natriuretic peptide (BNP) concentration of 400 pg/mL or more;
*Left ventricular ejection fraction (LVEF)<41% and left ventricular end diastolic diameter (LV-EDD)<56 mm (parasternal long-axis view) on echocardiogram;
*Increased troponin (3x upper reference limit [URL]) at the time of randomization;
*Clinical onset of cardiac symptoms within 3 weeks from randomization;
*Excluded coronary artery disease by coronary angiogram in subjects ≥46 years of age, in case myocarditis is not histologically proven;
*Randomization within 72 hours from hospital admission.

E.4

Principal exclusion criteria

*Known systemic autoimmune disorder or other conditions at the time of randomization where immunosuppression is assumed useful. Patients in whom a systemic autoimmune disorder will be diagnosed during hospitalization will be included in the study if randomized, including patients with a diagnosis of cardiac sarcoidosis or GCM). Both patients included in the corticosteroids-treatment arm or in the placebo-treatment arm can receive the standard immunosuppressive therapy used in the center since the diagnosis;
*Patients already on oral/IV chronic corticosteroid therapy or other chronic immunosuppressive therapies (colchicine or nonsteroidal
anti-inflammatory drugs [NSAIDs] are not considered immunosuppressive drugs);
*Contraindication to corticosteroids, including allergies to this medication and its excipients;
*Patients with peripheral eosinophilia (Eosinophil count >7% of the leukocytes) or known hypereosinophilic syndrome at the time of randomization. Patients in whom eosinophilic myocarditis will be diagnosed on EMB will be included in the study if already randomized. Both patients included in the corticosteroids-treatment arm or in the placebo-treatment arm can receive the standard immunosuppressive therapy used in the center since the diagnosis;
*Myocarditis associated with the ongoing administration of anti-cancer immune checkpoint inhibitor (ICI) agents;
*Previously known chronic cardiac disease (i.e., previous cardiomyopathy);
*Evidence of active bacterial or fungal infectious disease (presence of fever or increased C-reactive protein are not considered exclusion criteria), or suspected bacterial/fungal infection associated with increased levels of procalcitonin (cut-off >10 ng/mL), if the laboratory exam is available in the center;
*Known chronic infective disease, such as HIV infection or tuberculosis;
*Cardiac arrest before randomization or occurrence of out-of-hospital cardiac arrest;
* t-MCS instituted more than 48 hours before randomization;
*Patients clinically judged too sick to initiate t-MCS (i.e., irreversible multiorgan failure);
*Echocardiographic presence of images suggestive of other cardiac diseases (i.e. endocarditis)

*Participants involved in another clinical trial;
*Pregnant women (known pregnancy) or POSITIVE human chorionic gonadotropin (HCG) test measures (urine/blood) for women of 18-50 years of age.
*Any other significant disease with expected life expectancy <12 months or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial.

E.5 End points

E.5.1

Primary end point(s)

The Primary composite endpoint is defined as the time from randomization to the first event occurring within 6 months among: (1) all-cause death, or (2) HTx, or (3) long-term LVAD implant, Timepoint(s) of evaluation of this endpoint or (4) need for an upgrading of the t-MCS, or (5) a ventricular tachycardia (VT)/fibrillation (VF) treated with direct current (DC) shock (excluding VT/VF on t-MCS other than IABP), or (6) first rehospitalization due HF or ventricular arrhythmias or advanced AV block.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 0-3 of hospitalization
Day 5 of hospitalization
before discharge
2 months follow up
6 months followup

E.5.2

Secondary end point(s)

Secondary End Points:
1. The Main secondary composite endpoint is defined as the time from randomization to the first event occurring within 6 months among: (1) all-cause death or (2) HTx or (3) long-term LVAD implant or (4) first rehospitalization due to HF or ventricular arrhythmias or advanced AV block.
2. Mortality: time from randomization to all-cause death within 6 months.
3. In-hospital composite endpoint is defined as the proportion of patient who experience at least one of the following events during index hospitalization: (1) all-cause death, or (2) HTx, or (3) long-term LVAD implant, or (4) need for an upgrading of the t-MCS, or (5) a ventricular tachycardia (VT)/fibrillation (VF) treated with direct current (DC) shock (excluding VT/VF on t-MCS other than IABP).
4. Number of days on t-MCS from randomization.
5. Number of days in ICU from randomization.
6. Increase in LVEF on echocardiogram after 5 days from randomization (ECHO clips will be centrally reviewed in a blind fashion by readers).
7. 7. Relative reduction of troponin levels after 5 days from randomization (ratio of troponin level/local troponin upper reference limit [URL]).
8. Reduction in heart rate (HR) on ECG after 3 days from randomization (ECG recorded at the hour of initial randomization - ECGs will be centrally reviewed in a blind fashion by readers).
9. Proportion of patients with LVEF<55% AND/OR LV dilation on 6-month cardiac magnetic resonance imaging (CMRI) (CMRI clips will be centrally reviewed in a blind fashion by readers).
10. Proportion of patients with LVEF<55% on 6-month CMRI (CMRI clips will be centrally reviewed in a blind fashion by readers).
11. Proportion of patients with LV dilation on 6-month CMRI (CMRI clips will be centrally reviewed in a blind fashion by readers).

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 0-3 of hospitalization
Day 5 of hospitalization
before discharge
2 months follow up
6 months followup

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

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

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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:

270

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2022-04-04.

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

In case a patient is not able to sign an informed consent due to the ongoing AM,informed consent may be obtained, and information on the clinical trial may be given after the decision to include the subject in the clinical trial (deferred consent)

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

288

F.4.2.2

In the whole clinical trial

288

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

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

2022-04-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-19

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