E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent stenosis after correction of esophageal atresia |
Terugkerende stenosen na correctie van slokdarmatresie |
|
E.1.1.1 | Medical condition in easily understood language |
Recurrent narrowing of the esophagus after correction of a congenital discontinuity of the esophagus |
Terugkerende vernauwing van de slokdarm na de correctie van een aangeboren discontinuïteit van de slokdarm |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to find out whether intralesional steroid injections in children with esophageal atresia can prevent refractory strictures from developing and consequently can reduce the total number of dilatations needed within 28 days interval. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To compare between the two groups the level of dysphagia and the child’s eating behavior at the end of the follow up period. - To compare between the two groups the efficacy of dilatation with or without intralesional steroid injections on the luminal diameter and the stricture length. - To evaluate a possible influence of co-medication (e.g. antacids) on stricture formation. - To analyze the possible systemic effects of a one-time intralesional steroid injection. - To analyze the cost-effectiveness of the use of intralesional steroid injections to prevent refractory strictures. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The following patients are eligible for the study: - Children with EA type C who underwent primary anastomotic surgery within the first days of life - Age ≥3 months at the time of the 3rd dilatation - In need of a 3rd dilatation - Written informed consent by both parents or legal representatives, if applicable |
|
E.4 | Principal exclusion criteria |
The following patients are excluded from the study: - Age <3 months - Known inability from previous dilatations to use an endoscope with a size of 5.8 mm - No parental written informed consent |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome parameter is the total number of dilatations per patient within 28 days interval required during the study period, defined as the period from the day of the 3rd dilatation until 6 months later. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Six months after the intervention |
|
E.5.2 | Secondary end point(s) |
The secondary outcome parameters are: Total number of dilatations within the study period, regardless of the interval. Interval (in weeks) between the start of the study and the last dilatation procedure within the study period. Montreal Feeding Scale (in Dutch Screeningslijst Eetgedrag Peuters (SEP)), measured at the end of the follow up period. The relative change in maximal luminal diameter after the 3rd dilatation compared to the diameter before the 3rd dilatation. The relative change in length of the esophageal stricture after the 3rd dilatation compared to the length before the 3rd dilatation. The use of co-medication (e.g. antacids) during the study period. The mean cortisol level over the first three months after the 3rd dilatation, measured in a hair sample taken at the end of the follow up period. Total costs of the treatment, including medical and non-medical costs. Incremental costs per refractory stricture prevented and incremental costs per additional dysphagia-free patient.
Ad 2) The start of the study is defined as the day of the intervention, i.e. the interval is between the date of the 3rd dilatation and the date of the final dilatation. Ad 3) This scale has been validated and used in previous research in children with EA [41-43]. Ad 4, 5) Prior to the 3rd dilatation an esophagram is made to quantify the stricture, as standard of care. Two to three weeks after the 3rd dilatation another esophagram is made. This applies to both the intervention as the control group. An anterior-posterior and a lateral X-ray will be taken with the use of contrast. The diameter will be determined at the narrowest point of the esophagus. The length will be determined between the two points where the esophageal diameter starts narrowing. The diameter and length will be determined in both anterior-posterior and lateral direction. Earlier studies have proven that this is quite feasible from an esophagram [40]. All esophagrams will be reviewed in the coordinating hospital, by one specialized pediatric radiologist. The relative changes in diameter and length will be calculated by the following equations: "relative change in luminal diameter = " "maximal diameter after – maximal diameter before" /"maximal diameter before" "relative change in stricture length = " "stricture length after – stricture length before" /"stricture length before" Ad 6) All co-medication will be noted, if possible with doses and frequencies. Ad 7) In this hair sample the mean cortisol levels can be measured over the preceding six months with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantification of steroids [44]. This study will focus on the mean cortisol level over the first three months, with adjustment for age and sex. See the Standard Operating Procedure (SOP) document for more details. Ad 8, 9) The non-medical costs will be measured using the iMTA Productivity Cost Questionnaire (iPCQ), which is a validated questionnaire [45], supplemented with additional questions about the non-medical costs which are not included in the iPCQ. See Section 10.3 for further details on the cost-effectiveness analysis. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 months and 6 months after the intervention |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Dilatation without injection |
|
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 | Yes |
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
|
The trial is ended when 110 patients have been included and the last patient has completed the follow up period of 6 months. |
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |