Clinical Trial Results:
Delivering adequate nutrition to critically ill patients suffering delayed gastric emptying: RCT of nasointestinal feeding versus nasogastric feeding plus prokinetics.
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Summary
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EudraCT number |
2012-001374-29 |
Trial protocol |
GB |
Global end of trial date |
12 May 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Apr 2021
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First version publication date |
30 Apr 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Other trial identifiers |
Sponsor Reference: 2787 | ||
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Sponsors
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Sponsor organisation name |
North Bristol NHS Trust
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Sponsor organisation address |
Level 3, Learning & Research building, Bristol, United Kingdom, BS10 5NB
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Public contact |
Taylor, Stephen, +44 01173406581, stephen.taylor@nbt.nhs.uk
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Scientific contact |
Taylor, Stephen, +44 01173406581, stephen.taylor@nbt.nhs.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
21 Jan 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 May 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
12 May 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Delayed gastric emptying (DGE) commonly limits the use of enteral nutrition (EN) and may increase ventilator-associated pneumonia. Nasointestinal feeding has not been tested against dual prokinetic treatment (Metoclopramide and Erythromycin) in DGE refractory to metoclopramide. This trial tests the feasibility of recruiting this ‘treatment-failed’ population and the proof of concept that asointestinal (NI) feeding can increase the amount of feed tolerated (% goal) when compared to nasogastric (NG) feeding plus metoclopramide and erythromycin treatment.
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Protection of trial subjects |
Because critically ill patients cannot initially consent to treatment we asked their legally authorised representative
(relatives or clinician) to give consent then ask patients to consent to stay in the study, if and when they were able to do so.
Nasointestinal feeding necessitates placement of an additional tube. A guidance system was used to track placement in realtime, permitting tube withdrawal to prevent serious misplacement or trauma .
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Background therapy |
All patients received the best standard treatment regardless of whether they were in the study. | ||
Evidence for comparator |
The prokinetic group received continued treatment with metolcopramide in addition to treatment with erythromycin. Both drugs are routinely used as a prokinetic drugs in clinical practise. | ||
Actual start date of recruitment |
03 Dec 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 50
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Worldwide total number of subjects |
50
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EEA total number of subjects |
50
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
42
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
The study ran from 22/02/2013 to 12/05/2014 including 5 days follow up. | |||||||||||||||
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Pre-assignment
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Screening details |
Eligible patients were those who were mechanically ventilated and over 20 years old, with delayed gastric emptying (DGE). 1115 participants were screened. Of 208 patients with DGE, 77 were eligible, 2 refused assent, 25 had contraindications to intervention, almost exclusively prokinetic treatment, and it was feasible to recruit 50. | |||||||||||||||
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Period 1
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Period 1 title |
treatment allocation (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Blinding implementation details |
Intervention blinding was not possible because the of the requirement to use enteral tubes
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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NG Feed, metoclopramide and erythromycin | |||||||||||||||
Arm description |
NG Feed, metoclopramide & erythromycin 250mg IV 4x/d | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Metoclopramide
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Investigational medicinal product code |
CAS number; 7232-21-5 IMP no. PR3
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Other name |
Maxolon
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Discontinued 48h after gastric emptying adequate. 10mg per day. Total dose 30mg. Full Molecular formula: 4-amino-5-chloro-N-(2-(diethylamino)ethyl)-2-methoxybenzamide.
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Investigational medicinal product name |
Erythromycin
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Investigational medicinal product code |
CAS Number; 3847-29-8 IMP No. PR3
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Other name |
n/a
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
Maximum 250mg per day. Total dose 1000mg.
Full Molecular formula; 4-(dimethylamino)-3-hydroxy-6-methyloxan2-y-l]oxy}-14-ethyl-7, 1 2, 13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4, 6-dimet hyloxan-2-yl]oxy}-3,5,7,9,11,13-hexamethy-1-oxacyclotetradecan e-2,10-dione C37H67NO13
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Arm title
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EM-Guided NI Tube & Feeding, Stop Prokinetics | |||||||||||||||
Arm description |
EM-guided NI tube & feeding, stop prokinetics | |||||||||||||||
Arm type |
Alternative Treatment | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
NG Feed, metoclopramide and erythromycin
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Reporting group description |
NG Feed, metoclopramide & erythromycin 250mg IV 4x/d | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
EM-Guided NI Tube & Feeding, Stop Prokinetics
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Reporting group description |
EM-guided NI tube & feeding, stop prokinetics | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
NG Feed, metoclopramide and erythromycin
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Reporting group description |
NG Feed, metoclopramide & erythromycin 250mg IV 4x/d | ||
Reporting group title |
EM-Guided NI Tube & Feeding, Stop Prokinetics
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Reporting group description |
EM-guided NI tube & feeding, stop prokinetics | ||
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End point title |
Feed Goal Tolerated | ||||||||||||||||||||||||||||||
End point description |
All patients were increased from 40 mL feed/h or current rate to full rate whenever tolerated. Tolerance was defined GRVs <250 mL and no vomiting in the prokinetic group and where GRVs contained no macroscopic feed in the NI group. The first GRV 250 mL was discarded and EN was continued at the same rate but a second consecutive 4 hourly GRV 250 mL was discarded and the feed rate was reduced 50%. Ileus triggered cessation of EN and 4 hourly re-assessment for risk of bowel ischaemia.
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End point type |
Primary
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End point timeframe |
Over the 5 days of the intervention or up to the point of death.
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Statistical analysis title |
% Feed Goal Tolerated between groups | ||||||||||||||||||||||||||||||
Statistical analysis description |
‘blind to intervention’, intention-to- treat analyses. Normality was determined by a ShapiroeWilks test (p<0.05) and an independent samples Student's t test or ManneWhitney test as appropriate. The 95% confidence intervals (95%CI) refer to the mean or median difference between treatment groups in the respective tests. Categorical data was analysed using Fisher's exact test.
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Comparison groups |
EM-Guided NI Tube & Feeding, Stop Prokinetics v NG Feed, metoclopramide and erythromycin
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Number of subjects included in analysis |
50
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||||||||||||||||||||
P-value |
= 0.026 [2] | ||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||||
Confidence interval |
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| Notes [1] - Effect sizes ([mean of intervention e control]/ standard deviation) and bootstrapped 95%CI for medians were calculated and presented with the percentage difference between intervention and control. Analyses for continuous and categoricalvariables were done using Cohen's d and Cramer's V tests, respectively. A ManneWhitney test was used to determine the difference of the area under the curves of feed goal (%), to provide an overall pvalue over the 5 days of the intervention or up to death. [2] - (Median [IQR] 432 [253-464]% vs. 350 [213-381]%) |
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Adverse events information
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Timeframe for reporting adverse events |
22/05/2013 - 12/05/2014
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15
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Reporting groups
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Reporting group title |
NG Feed, metoclopramide and erythromycin
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Reporting group description |
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Reporting group title |
EM-Guided NI Tube & Feeding, Stop Prokinetics
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Limitations of this study include inability to perform ‘intervention blinding’ or quantify gastric emptying, introducing potential bias and reducing the efficacy in recruiting the target group, respectively. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/28531392 |
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