NCT02435069

A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children

Completed Phase 4 Results posted Last updated 28 August 2019

What this trial tests

Phase 4 trial testing Dose Response - NS and USP Glycerin - First Intervention in Fecal Incontinence in 5 participants. Completed in 30 March 2018.

Timeline

9 February 2016

Primary endpoint
28 March 2017

30 March 2018

Quick facts

Lead sponsor	Nemours Children's Clinic
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	supportive care
Enrollment	5
Start date	9 February 2016
Primary completion	28 March 2017
Estimated completion	30 March 2018
Sites	1 location across United States

Drugs / interventions tested

• Dose Response - NS and USP Glycerin - First Intervention — full drug profile →
• Effectiveness - NS and USP Glycerin - Second Intervention — full drug profile →

Conditions studied

• Fecal Incontinence — all drugs for Fecal Incontinence →
• Neurogenic Bowel — all drugs for Neurogenic Bowel →

Sponsor

Nemours Children's Clinic

Who can join

Adults 3 to 12, any sex, with Fecal Incontinence or Neurogenic Bowel. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen Primary · Data collection started following consent and procedural training and was collected daily from day 1 for the duration of the study, an average of 135 days.

Fecal soiling was defined as non-toilet elimination, which was tracked and documented by the parent/child as direct event recording and tallied as the number of pairs of underwear/protective undergarments soiled with stool per day. The purpose of this outcome measure was to document the number of individuals who gained continence on NS and USP glycerin. Descriptive statistics was limited to percentage of total participants who achieved continence on each flushing regimen. Data was calculated on the last data point in the final phase for both the NS and USP glycerin flush.

Group	Value	95% CI
Subjects Continent on NS Antegrade Flush	1
Subjects Continent on USP Glycerin	4

Fecal Soiling - Quantitative Count Detailing the Number of Episodes of Fecal Incontinence Per Day on NS and USP Glycerin Primary · Data collection began following consent and procedural training and was collected daily from day 1 for the duration of the study, an average of 135 days.

Fecal soiling was defined as non-toilet elimination, which was tracked and documented by the parent/child as direct event recording and tallied as the number of pairs of underwear/protective undergarments soiled with stool per day. Descriptive statistics included mean and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05, calculated on the data from the last day of the completed NS and USP Glycerin phases of the study. Power analysis conducted using data from this study with α = 0.5,

Group	Value	95% CI
Episodes of Fecal Incontinence on NS Antegrade Flush	2	± 1.87
Episodes of Fecal Incontinence on USP Glycerin Antegrade Flush	0.2	± 0.45

NS and USP Glycerin Flush Solution Dosing Frequency Necessary to Achieve Continence Secondary · Frequency of administration data was collected as the total number of flushes recieved over the last three days of each dosing phase for both NS and USP Glycerin and recorded as either daily (1), every other day (2), or every third day

Flush administration frequency necessary to achieve continence was recorded as a single measure per subject per flush solution obtained as the number of flushes in the last three days of each dosing phase and recorded as either daily (1), every other day (2), or every third day (3). The larger the value, the less frequent the flush, the better the clinical outcome. Dosing frequency was measured using direct observational recording completed by the parent or child. Descriptive analysis included mean, and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, t

Group	Value	95% CI
Dosing Frequency on NS	1	± 0
Dosing Frequency on USP Glycerin	1.6	± 0.894

Flush Volume Secondary · Data for analysis was collected from the last flush of the NS and USP Glycerin dosing phase of the study

Flush volume was measured in mL/flush using a graduated cylinder and recorded by the parent or child with each flush and later calculated in mL/kg. Data derived from the last flush of the completed dosing phase of both NS and USP Glycerin were used to calculate flush volume. Descriptive analysis included mean, median, range, and standard deviation. Reported data excludes subjects who failed to gain and maintain continence on either flushing regimen.

Group	Value	95% CI
Flush Volume of NS	39.215	± 12.424
Flush Volume of USP Glycerin	1.475	± 0.457

Number of Participants With Any Electrolyte Abnormality Secondary · Collection dates included a baseline sample (week 1) and at the completion of the dosing trail for both NS and USP glycerin for a total of 3 samples

Evaluated impact of NS and USP Glycerin antegrade flush on serum electrolytes using a blood test called a Basic Metabolic Panel. Data analysis limited to percentage of subjects demonstrating any electrolyte abnormality on NS or USP glycerin.

Group	Value	95% CI
Elelctrolye Abnormalities on NS FLush	0
Elelctrolye Abnormalities on USP Glycerin FLush	0

Change in Stool Calprotectin Levels Assessed Through Comparing Levels Obtained Following Completion of NS and USP Glycerin Dosing Phases With the Baseline Value For Each Subject Secondary · Collection dates included a baseline sample (week 1) and at the completion of the dosing trail for both NS and USP glycerin for a total of 3 samples

Stool calprotectin was used to evaluate the impact of NS and USP Glycerin antegrade flush on colonic health. Calprotectin levels were obtained at baseline and following completion of the NS and USP Glycerin dosing phase of the study. Descriptive data analysis included mean and standard deviation for each flush regimen. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Both descriptive and inferential data analysis was calculated on the difference in calprotectin levels between samples obtained at basel

Group	Value	95% CI
Calprotectin Levels Following NS FLush	133.7	± 183.359
Calprotectin Levels Following USP Glycerin FLush	108	± 113.874

Cramping With Flush Secondary · Data analysis was completed on data obtained during the last flush in both the NS and USP Glycerin dosing phase

Cramping with flush was measured using the Wong Baker Faces Pain Rating Scale (WBFPRS). The WBFPRS has undergone extensive testing and has well established psychometrics in the pediatric population. The scale ranges from 0 (very happy without pain) to 10 (the worse pain imaginable). Each pain level is associated with a facial expression. The child is asked to choose the face that best describes his/her level of discomfort (ordinal data). The parent was instructed to call if the child had flushing regimen-associated discomfort greater than a 4 on the WBFPRS. Documentation of pain severity was c

Group	Value	95% CI
Pain With NS Antegrade Flush Administration	0	± 0
Pain With USP Glycerin Antegrade Flush Administration	0.4	± 0.89

Number of Participants Experiencing Vagal Symptoms With Flush Secondary · Data collection started with the first flush administered following discharge from the hospital and was collected with every subsequent flush through completion of the study, an average of 115 days.

Vagal symptoms including nausea, vomiting, sweating, dizziness, and pallor were noted by the parent. The parent was instructed to call if the child had any vagal symptoms. Documentation of any vagal symptoms was completed by the parent and child on a data-collection form at the time of occurrence. Data was analyzed as a percentage of subjects experiencing vagal symptoms during flush with NS and USP glycerin.

Group	Value	95% CI
Vagal Symptoms With NS FLush	0
Vagal Symptoms With USP Glycerin Flush	1

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year 1 month. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vagal Symptoms With NS Flush

Serious: 0/5 (0%)

Deaths: 0/5

Vagal Symptoms With USP Glycerin Flush

Serious: 0/5 (0%)

Deaths: 0/5

Other adverse events (1 terms — click to expand)

Reaction	System	Vagal Symptoms With NS Flush	Vagal Symptoms With USP Gl…
Vasovagal Response	Vascular disorders	—	—

Data from ClinicalTrials.gov NCT02435069 adverse events section.

Sponsor's own description

There is a surgical procedure to help children with intractable fecal incontinence gain continence for stool through construction of a tube that connects the abdominal wall to the colon near or through the appendix. This tube allows easy administration of enema solution into the first part of the colon. Putting enema solution through that tube into the colon is called an antegrade continence enema (ACE) and has been shown to work well in helping some but not all children prevent stool accidents. The purpose of this study is to compare a large volume ACE flush using a salt water solution called normal saline with a small volume ACE flush using liquid glycerin. The aims of this study are to: 1) find the most effective dose and flush frequency of each solution needed to prevent stool accidents; 2) compare which solution given at the best dose has the least side effects and 3) to determine if administration of either of the ACE flushing solutions causes electrolyte abnormalities or affects colon health.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.