E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007540 |
E.1.2 | Term | Cardiac disorder NOS |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) To implement hyperpolarized [13C]-pyruvate cardiac MR to successfully image metabolic flux in the human heart.
2) To investigate whether specific "metabolic fingerprints of the failing heart" differentiate patients with different severities of heart failure.
3) To determine metabolic changes in the failing human heart before and after optimization of medical heart failure treatment.
4) To investigate if hyperpolarized [13C]-pyruvate cardiac MR metabolic fingerprints can differentiate responders from non-responders to medical treatment. |
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E.2.2 | Secondary objectives of the trial |
To establish whether the sensitivity of MR-hyperpolarized [1-13C]Pyruvate based MR-spectroscopy is high enough for future studies of therapy effects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Dilated Cardiomyopathy
> 18 years of age.
Diagnosis of Dilated Cardiomyopathy (DCM)
Left ventricular Ejection Fraction (LVEF) of 10 – 45 %
Adequate hematologic and organ function, i.e.
ANC at least 1.500/uL
Platelet count >100/uL
Se bilirubin <1.5 UNL
ASAT, ALAT and AP up to 2.5 x UNL
Se creatinine up to 1.5 x UNL or creatinine clearance at least 30 ml/min
INR and aPTT at most 1.5 x UNL, except for patients on AK treatment
Women who are not postmenopausal or surgically sterile must have a negative serum or urine pregnancy test performed at time of inclusion in the study. Safe and highly effective contraception must be used throughout the study meaning either hormonal anti-conception or an anti-fertility intrauterine device. If the partner is non fertile or the patient has no sexual activities, this is also accepted.
Danish speaking
Able and willing to comply after informed consent |
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E.4 | Principal exclusion criteria |
Not able or willing to receive heart failure therapy
Patients not willing to participate
Uncontrolled serious medical condition, such as uncontrolled heart
disease, uncontrolled diabetes, intestinal obstruction, uncontrolled
hypertension, or recent cerebral ischemia
Receiving more than 50% of taget dose of ACE-inhibitor and
betablockers before inclusion
Previous heart surgery including PCI
Estimated Glomerular Filtration Rate (eGFR) <30 mL/min
Diabetes Mellitus
Intolerance to Pyruvate |
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E.5 End points |
E.5.1 | Primary end point(s) |
The scanning program is terminated after 20 patients have been examined before and after uptitration in heart failure medication using the MR-hyperpolarization scanning technique |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final endpoint is reached when the planned examinations are completed. Additionally, if two or more at least grade three AEs related to C13-Pyruvate occur at the established dose level of 0.43 mg/kg among the first 5 patients, the dose of 13C-Pyruvate will be reduced. If two or more at least grade three AEs related to the drug occur at the reduced dose level in the subsequent five patients, the experiment will be disrupted. If grade four AEs or any SAEs related to the drug occur, each event will be reviewed by the protocol group with respect to safety and consideration of study disruption |
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E.5.2 | Secondary end point(s) |
intermediate endpoints relate to sensitivity of the hyperpolarised scanning technology for demonstrating therapy effects |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After the first five patients are hypperpolarization data examined for expected sensitivity of the applied scanning technology. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |