E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Ocular Physiological Phenomena [G14] |
MedDRA Classification |
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 |
The primary objective is to evaluate the efficacy of low dose (0.01%) atropine eye drops to slow the progression of short-sightedness in UK children after 24 months of treatment.
|
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are: • To evaluate the safety and tolerability of low dose atropine eye drops • To determine how the atropine eye drops work to slow the progression of short-sightedness in children
The exploratory objective is to explore the influence of other factors in the progression of short-sightedness, including hours of outdoor activity, use of spectacles for correction of vision, iris colour, ethnicity, and family history. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
In order to assess the effects on recruitment of local media (radio) advertisement, we will conduct a Study Within A Trial (SWAT) three and six months after commencing recruitment. We will compare the effects on recruitment using two interventions: local radio advertisement (for two weeks) 3 months after starting recruitment in two randomly chosen sites; and local radio advertisement (for two weeks) 6 months after starting recruitment in two randomly chosen sites. The primary outcome will be the change in recruitment after the radio advertisement compared to before the advertisement. Secondary outcomes will be retention of participants in the trial, and changes in the number of potentially eligible participants who are assessed or approached for the trial.
A SWAT to explore study drug adherence by comparing a non-expensive and pragmatic method of adherence assessment i.e. bottle weighing, with the electronic adherence monitoring data captured from a Medical Events Monitoring System (MEMS). At one site (Belfast), eye drop bottles will be weighed on calibrated scales in the pharmacy department at the time of dispensing and again on return to pharmacy at the end of the six-month treatment period.
A novel recruitment method will be investigated through embedding the TRECA (TRials Engagement in Children and Adolescents) study within the CHAMP UK trial. TRECA is investigating whether providing children and young people with information about a trial through a multimedia information (MMI)resources impacts on recruitment and retention rates as well as the quality of decision-making about trial participation. TRECA is funded by the NIHR (HS&DR 14/21/21), with ethical and HRA approval already obtained. The MMIs are websites with text, images, animations and videos about the CHAMP UK trial. Phase one of TRECA saw the development of the MMIs, through participatory design and usability testing with children and adolescents with long-term health conditions, their parents and clinicians. The MMIs will be based on information from the CHAMP UK PIS. The MMIs also include generic animations that cover elements about trials, including: • what is a trial? • why do we do trials? • who is in a research team • assent and consent In addition, the CHAMP UK MMIs will have an explainer animation about the study on the front/home page of the MMI. The idea is that this explainer covers the main features of the trial in approximately 60 seconds of animation. Individuals approached to participate in CHAMP UK will be randomly allocated to receive either: • the standard PIS, or • the CHAMP UK MMI, developed by TRECA in conjunction with the CHAMP UK study team, or • both the MMI and PIS
|
|
E.3 | Principal inclusion criteria |
1. Age 6-12 years (at the time of consenting) 2. Myopia of -0.5D or greater (spherical equivalent refractive error) in both eyes 3. Best-corrected distance visual acuity (BCDVA) of 0.20 logMAR or better in both eyes
|
|
E.4 | Principal exclusion criteria |
1. Children with other ocular morbidities 2. Myopia of -10D or greater in either eye 3. Astigmatism of 2D or higher in either eye 4. Amblyopia 5. Significant health problems that can compromise the ability to attend research visits or complete the trial 6. Other factors that may compromise the ability to attend the research appointments 7. Parents or children with poor understanding of the English language 8. Children enrolled in other interventional trials 9. Allergy or hypersensitivity to atropine or excipients |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is spherical equivalent refractive error (SER) (i.e. myopia severity) of both eyes after 24 months measured by autorefractor under cycloplegia, adjusted for baseline. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Participants will attend a total of five research visits; the first will be the baseline visit. Participants will then attend a research visit every six months for the duration of the study.
-Baseline -Month 6 -Month 12 -Month 18 -Month 24 |
|
E.5.2 | Secondary end point(s) |
Secondary Outcomes - Central axial length: measured using a laser biometer at central fixation conditions - Best corrected distance visual acuity (BCdVA) (uniocular and binocular): assessed using the logMAR ETDRS chart. This is a standard letter chart used in research to ensure accuracy and validity of the acuity measurements and has been shown to be repeatable in children (Manny 2003) - Near visual acuity (uniocular and binocular): tested using near logMAR ETDRS at 40 cm - Reading speed: measured with the Wilkins Rate of Reading test - Pupil diameter: measured using an autorefractor - Accommodation: measured prior to the instillation of cycloplegia using the autorefractor. The measures will be taken monocularly in each eye and binocularly (minimum 3 measurements per condition). The accommodation response (accommodation lag) will be determined by calculating the difference between the Accommodation Response (AR = near MSE (autorefractor)) and the Accommodation Stimulus - Spectacle correction - Tolerability: using a 4-point scale to quantify, from the point of view of the participant, (1) local irritation/stinging associated with eye drop instillation; (2) photophobia; and (3) difficulties reading and writing - Adverse event rates and allergic reactions rates. - Quality of Life: measured using the EQ-5D-Y
Exploratory Outcomes/Mechanistic Evaluations - Peripheral axial length: measured using a laser biometer at peripheral fixation conditions - Peripheral retinal defocus: measured with the autorefractor at central and peripheral fixation conditions - Anterior chamber depth: measured with a laser biometer - Iris colour: measured using a visual grading scale of dark brown, light brown, blue, green, grey - Height and weight to provide information about the links between the child’s development and eye growth and potentially information about lifestyle - Hours of outdoor activity: measured using an activities questionnaire - Ciliary body biometry: measured using anterior-segment OCT (AS-OCT). This will enable changes in lens position and ciliary muscle changes resulting from atropine use to be compared with normal myopic growthChorio-retinal thickness: measured using spectral domain OCT (SR-OCT). This will enable differences in choroidal thickness resulting from atropine use to be compared with normal myopic growth |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Central axial length–Baseline, Months 6, 12, 18 & 24 BCdVA–Baseline, Months 6, 12, 18 & 24 Near visual acuity–Baseline, Months 6, 12, 18 & 24 Reading speed–Baseline, Months 6, 12, 18 & 24 Pupil diameter–Baseline, Months 6, 12, 18 & 24 Accommodation–Baseline, Months 6, 12, 18 & 24 Spectacle correction–Baseline, Months 6, 12, 18 & 24 Tolerability–Months 6, 12, 18 & 24 Adverse event rates–Months 6, 12, 18 & 24 Quality of Life–Baseline, Months 6, 12, 18 & 24 Peripheral axial length–Baseline, Months 12 & 24 Peripheral retinal defocus–Baseline, Months 12 & 24 Anterior chamber depth–Baseline, Months 6, 12, 18 & 24 Iris colour–Baseline Height & weight– Baseline, Months 6, 12, 18 & 24 Hours of outdoor activity–Baseline, Months 6, 12, 18 & 24 Ciliary body biometry–Baseline, months 1 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 4 |
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
|
For the purposes of submitting the end of trial notification to the Sponsor and the Research Ethics Committee (REC), the end of trial will be considered to be when the database lock occurs for the final analysis. The trial will be stopped prematurely if: • Mandated by the REC • Mandated by the Sponsor (e.g. following recommendations from the TSC • Funding for the trial ceases This is to ensure that all data has been cleaned, quality controlled and monitored prior to analysis. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 31 |