About this trial

This is a multi-centre, open-label, single-dose safety, tolerability and PK-pharmacodynamics (PD) study of the vasodilator regadenoson in 3 paediatric age groups for whom a pharmacologic stress perfusion CMR test is clinically indicated; adolescents aged 12 to \<18 years (Cohort A), children aged 2 to \<12 years (Cohort B), and infants aged 1 to \<24 months and who weigh at least 3 kg (Cohort C). Regadenoson will be used as the pharmacologic stress agent in this study with MPI serving as both surrogate pharmacodynamic marker of the agent (MPR, MBF) and a clinically evaluable examination for the patient

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

* Male or female adolescent aged from 12 to <18 years (Cohort A) or child aged from 2 to <12 years (Cohort B) or infant aged from 1 to <24 months (Cohort C).

Patient weighs at least 3 kg.

Patients who need to undergo a clinically indicated pharmacologic stress perfusion CMR test and who are considered fit for a pharmacological stress perfusion CMR by the investigator. The pharmacologic stress perfusion CMR may be performed in patients for further evaluation of cardiovascular conditions or diseases, such as, but not limited to, Kawasaki disease, congenital heart diseases, congenital coronary abnormalities, and post-cardiac surgery / transplantation, etc.

Stable medication regimen for at least 7 days prior to dosing. Stable is defined as no addition, discontinuation, or change of any medications (or their doses), that could alter the rate-pressure product (HR x BP).

Disqualifiers

* Prior allergic reaction to Gd contrast agents and/or regadenoson or any component of its formulation, or to aminophylline or to its components (ethylenediamine and theophylline).

Standard clinical contraindications to MRI as per institutional guidance, including patients with cochlear implants and implanted cardiac devices, or considered unfit for a pharmacologic stress perfusion CMR test by the investigator.

All patients will be screened for eGFR within 24 hours before the exam and patients presenting with eGFR <30 mL/min/1.73 m2 (by the Schwartz formula) will be excluded.

Pregnant or lactating females, or females of childbearing potential not using an acceptable form of birth control (negative urine pregnancy test also required).

Trial design

Design model

Sequential

Treatments tested in this trial

Regadenoson
Drug
Regadenoson (Rapiscan®): Single i.v. bolus dose in stress rest CMR

Treatment groups

54 Participants

are divided into 3 treatment groups

Group A: adolescents aged 12 to <18 yearsExperimental treatment 1 intervention

Group B: children aged 2 to <12 yearsExperimental treatment 1 intervention

Group C: infants aged 1 to <24 months and who weigh at least 3 kgExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Occurrence of Adverse Events (AEs) following administration of Regadenoson

An overall summary of AEs, SAEs, and Regadenoson-emergent AEs will be presented, coded using the Medical Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class and preferred term.

Time frame

70 hours after Regadenoson administration

2

Changes in physical examinations following administration of Regadenoson

The number of patients with changes in physical examination status from normal at baseline to abnormal at each post-administration time point will be summarized.

Time frame

Baseline and 2 hours after Regadenoson administration

3

Changes in physical examinations following administration of Regadenoson

The percentage of patients with changes in physical examination status from normal at baseline to abnormal at each post-administration time point will be summarized.

Time frame

Baseline and 2 hours after Regadenoson administration

4

Changes in oxygen saturation following administration of Regadenoson

The occurrence of post-administration vital sign values outside the normal limits will be summarized.

Time frame

Baseline, 15 and 5 minutes before Regadenoson administration and 1, 3, 6, 10, 15, 30 minutes and 1, 2 hours after Regadenoson administration

Secondary outcomes

1

Determine the correlation between regadenoson PK concentration (ng/mL) and changes in HR (bpm), including impact of patient factors.

The correlation between regadenoson PK concentration and change in HR at different time points will be evaluated using compartment methods and a population approach with mixed-effect modelling adjusted for patient factors.

Time frame

1, 3, 5, 10, and 20 minutes and 1 and 2 hours post Regadenoson administration

2

Determine the associated myocardial hyperaemic response after administration of regadenoson using dynamic first-pass perfusion magnetic resonance imaging (MRI).

The Myocardial perfusion reserve (MPR) and Myocardial blood flow (MBF) values derived from the quantitative image analysis of the myocardial perfusion images will be listed per patient and summarized with descriptive statistics by age group and actual dose.

Time frame

1 hour post Regadenoson administration.

3

Determine the associated myocardial hyperaemic response after administration of regadenoson using dynamic first-pass quantitative myocardial perfusion reserve (MPR) analysis.

The Myocardial perfusion reserve (MPR) and Myocardial blood flow (MBF) values derived from the quantitative image analysis of the myocardial perfusion images will be listed per patient and summarized with descriptive statistics by age group and actual dose.

Time frame

1 hour post Regadenoson administration.