Esophageal motility disorders and gastroesophageal reflux in ventilated critically ill patients with different feeding tolerance: effect of prokinetics
| ISRCTN | ISRCTN14399966 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14399966 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | Nil known |
| Sponsor | Charles University Faculty of Medicine in Pilsen |
| Funders | Ministry of Health, Czech Republic - conceptual development of research organization (Faculty Hospital in Pilsen - FNPl, 00669806), The Charles University Research Fund (project no.Q39), Grant for “Fighting Infectious Diseases” awarded by the MEYS CR and financed by the EFRR project [CZ.02.1.01/0.0/0.0/16_019/0000787] |
- Submission date
- 27/08/2020
- Registration date
- 03/09/2020
- Last edited
- 06/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
High-resolution impedance manometry (HRIM) is the most modern method to measure motility (contractions) of the esophagus and its sphincters while also measuring impedance, which is able to detect the reflux (backflow) of fluid and gas from the stomach to the esophagus. However, esophageal functions in mechanically ventilated critically ill patients have not yet been studied using HRIM.
The study aims to characterize the key general features of esophageal motility functions using HRIM in mechanically ventilated critically ill patients. Second, to compare the pattern of abnormal esophageal physiology and gastroesophageal reflux in patients with low residual gastric volumes and high residual gastric volumes. Third, to evaluate the effects of metoclopramide and compare it to healthy controls. Finally, to determine the safety and feasibility of HRIM in critically ill patients.
Who can participate?
Participants in the study are critically ill adult patients and adult healthy volunteers as a control group.
What does the study involve?
Critically ill patients in need of respiratory support, who are recovering from the original insult and are already receiving full nutrition via a nasogastric tube (25 kcal / kg / day) and who also meet the inclusion criteria are classified into two arms: 1 / those who tolerate nutrition poorly, i.e. their regularly measured nutritional residues in the stomach exceed 500ml / 24 hours before inclusion in the study and 2 / those who tolerate nutrition well, i.e. residues not exceeding 100ml / 24 hours. On the day of the study, during sedation a manometric-impedance (HRIM) catheter is inserted along the nasogastric tube so that both the upper and lower esophageal sphincters and stomach cardia are visible in the recording window. After a 1-hour period of steady state, HRIM study data are collected for 5 hours together with detailed clinical and laboratory monitoring, metoclopramide 10 mg is administered intravenously after the first 2 hours of measurements.
In the control group, the HRIM catheter is inserted after 4 hours of fasting and first the esophageal functions are measured at rest. Then dynamic measurements are recorded upon swallowing 5 ml of saline (at least 7 valid swallows recorded). This is the fasting phase of measurements. After eating the study meal (250ml of nutrition drink) the postprandial phase is recorded, subsequently, metoclopramide 10 mg is administered intravenously and after a 5-minute pause the intervention phase is recorded. The study ends with extraction of the manometric catheter.
The only follow-up is ICU and hospital mortality. No drugs or invasive procedures out of the ordinary practice are used during this study.
What are the possible benefits and risks of participating?
In critically ill patients the obtained data can help optimize the treatment of the ongoing disease, or by adjusting the nutritional regime and its administration prevent the development of pneumonia, which can complicate mechanical ventilation. In control subjects, the standard manometric examination of the esophagus can detect possible axial hiatal hernia.
The potential risks include a discomfort resulting from nasal catheter insertion that will be addressed by administering a small dose of sedative or by catheter insertion in the early morning if sedatives are administered to induce night sleep. The catheter is thin and soft so any injury to the nose or nasopharynx during insertion is unlikely though it cannot be completely ruled out. The second potential risk is administering one dose of metoclopramide 10 mg intravenously. With the usual therapeutic doses of metoclopramide, side effects are rare and mild and transient. Fatigue, drowsiness, restlessness may occur frequently (approximately 10% of patients). Uncommonly, insomnia, headache, confusion, dizziness or mental depression, indigestion, urticaria and dry mouth may occur. Rarely (0.2% of patients), extrapyramidal side effects occur and, in most cases, manifest as acute dystonia. In practice, side effects are very rarely observed in critically ill patients.
All possible adverse events are registered, recorded and treated in accordance with the requirements of good clinical practice. Possible adverse events are reported to the State Institute for Drug Control in the standard manner. Each subject with a reported adverse event will be followed up and the progression of the adverse event will be monitored until it resolves, stabilizes, or is stated with certainty that it has no causal relationship to the study interventions. At the same time, any measures will be taken to resolve the adverse event according to the decision of the attending physician.
Where is the study run from?
Pilsen University Hospital (Czech Republic)
When is the study starting and how long is it expected to run for?
April 2012 to March 2016
Who is funding the study?
1. Ministry of Health (Czech Republic)
2. Charles University Research Fund (Czech Republic)
3. Ministry of Education, Youth and Sport of the Czech Republic (Czech Republic)
Who is the main contact?
Dr Karel Balihar
balihar@fnplzen.cz
Contact information
Scientific
1st Department of Internal Medicine
Faculty of Medicine in Pilsen
Pilsen University Hospital
Charles University Prague
Alej Svobody 80
Pilsen
32300
Czech Republic
 ORCID ID |
0000-0002-1940-983X |
|---|---|
| Phone | +42 0720375344 |
| balihar@fnplzen.cz |
Public
1st Department of Internal Medicine
Faculty of Medicine in Pilsen
Pilsen University Hospital
Charles University Prague
Alej Svobody 80
Pilsen
32300
Czech Republic
| ORCID ID |
0000-0002-1940-983X |
|---|---|
| Phone | +42 0720375344 |
| balihar@fnplzen.cz |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Explorative prospective single-center controlled comparative study with pharmacological intervention |
| Secondary study design | Non randomised study |
| Participant information sheet | ISRCTN14399966_PIS_Control_05Sep20.pdf |
| Scientific title | Esophageal dysmotility and gastroesophageal reflux in adult ventilated critically ill patients with low and high residual gastric volumes and how it is affected by intravenously administered metoclopramide: a controlled, single center, prospective study using high resolution impedance manometry |
| Study objectives | 1. Mechanically ventilated critically ill patients have impaired esophageal function compared to healthy subjects 2. The degree of esophageal dysfunction (motility, sphincter tone, reflux episodes) correlates with the degree of clinically determined upper gastrointestinal dysfunction (residual volume from nasogastric tube) 3. Metoclopramide improves lower esophageal sphincter tone and reduces the number of reflux episodes 4. Esophageal HRIM is safe and feasible in critically ill patients |
| Ethics approval(s) | Approved 07/06/2012, Local Ethical Committee at the Faculty Hospital in Pilsen (Edvarda Benese 13, 305 99, Pilsen, Czech Republic; +420 377 423 275; snebergerova@fnplzen.cz), ref: 230/2012 |
| Health condition(s) or problem(s) studied | Esophageal dysmotility and gastroesophageal reflux in ventilated critically ill patients |
| Intervention | Critically ill hemodynamically stable patients fulfilling inclusion/exclusion criteria within 24-48 hours after reaching the enteral nutrition target of 25 kcal/kg/day are assigned according to residual gastric volumes to the low gastric volumes group (up to 100 mL/24h of gastric residual volume from nasogastric tube) or high gastric volumes group (more than 500 mL/24h). After calibration, high resolution impedance manometry (HRIM) catheter is inserted along the nasogastric tube so that both the upper and lower esophageal sphincters and stomach cardia are visible in the recording window. After a 1-hour period of steady state, HRIM study data are collected for 5 hours together with detailed clinical and laboratory monitoring. Metoclopramide 10 mg i.v. is administered after the first 2 hours of measurements. There are no differences in the intervention in the low gastric volumes group and the high gastric volumes group. Variables are measured during a 6 hour period on the day of the study, from 6 a.m. to 12 a.m. 6:00 a.m. - 7:00 a.m. measurement of High resolution impedance manometry (HRIM) at steady state, 7:00 a.m. - 9:00 a.m. native HRIM, 9:00 a.m. - 12:00 a.m. HRIM after metoclopramide administration. Control group subjects are healthy volunteers who agreed to participate in the study and fulfilled the inclusion and exclusion criteria. In the control group, the fasting phase HRIM is first recorded and analyzed according to Chicago classification version 3.0, then, after eating the study meal the postprandial phase is recorded and analyzed using the same protocol, subsequently metoclopramide 10 mg is administered intravenously and after a 5-minute pause the intervention phase is recorded. The study ends with extraction of the manometric catheter. The only follow-up is ICU and hospital mortality in critically ill patients. No blinding or randomization is performed. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Metoclopramide |
| Primary outcome measure(s) |
1. To characterize esophageal dysfunction in critically ill patients in comparison to physiologic conditions and to verify whether the administration of a prokinetic is effective in improving esophageal dysfunction in critically ill patients using: |
| Key secondary outcome measure(s) |
1. Feasibility and safety of performing HRIM in critically ill patients measured using the percentage of: cases of successful HRIM catheter insertion; and type of complications of insertion of HRIM catheter (such as epistaxis) |
| Completion date | 31/03/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 30 |
| Total final enrolment | 16 |
| Key inclusion criteria | Critically ill patients 1. Informed consent signed by a close relative and retrospectively by the patient when his/her condition allows it 2. Age of 18 years and above 3. Mechanically ventilated critically ill patient 4. Inclusion within 24-48 hours after reaching the enteral nutrition target of 25 kcal/kg/day 5. Maximum stable dose of noradrenaline up to 0.2 µg/kg/min 6. Enteral nutrition via nasogastric tube Control group 1. Signed informed consent 2. Age of 18 years and above |
| Key exclusion criteria | Critically ill patients: 1. History of previous surgery on upper gastrointestinal tract 2. Gastroesophageal reflux disease 3. Portal hypertension 4. Active gastrointestinal bleeding 5. When an acute diagnostic or treatment procedure outside the intensive care unit at the time of HRIM measurements is required 6. Epilepsy, severe CNS damage or other contraindication for metoclopramide administration 7. Coagulopathy with INR value above 2.5 and platelets below 30x10e9/L 8. Pregnancy Control group 1. History of previous surgery on upper gastrointestinal tract 2. Diagnosed gastroesophageal reflux disease or symptoms thereof, esophageal varices, or other organic esophageal or gastric disorder 3. Use of chronic medication, other acute or chronic illness 4. Pregnancy |
| Date of first enrolment | 23/01/2013 |
| Date of final enrolment | 24/02/2016 |
Locations
Countries of recruitment
- Czech Republic
Study participating centre
Faculty of Medicine in Pilsen
Charles University Prague
Alej Svobody 80
Pilsen
304 60
Czech Republic
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The data that support the findings of this study will be available from the corresponding author upon reasonable request (email: balihar@fnplzen.cz ). Supporting data will be made available to Editorial Board Members and referees at the time of submission for the purposes of evaluating the manuscript and directly upon request to any reader on and after the publication date. Supporting datasets will be made available as Supplementary Information files that will be freely accessible on the journal´s website upon publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 08/02/2021 | 10/02/2021 | Yes | No |
| Participant information sheet | 05/09/2020 | 05/09/2020 | No | Yes | |
| Participant information sheet | 05/09/2020 | 05/09/2020 | No | Yes | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | 06/11/2023 | No | No |
Additional files
- ISRCTN14399966_PIS_Control_05Sep20.pdf
- Uploaded 05/09/2020
- ISRCTN14399966_PIS_Criticallyill_05Sep20.pdf
- Uploaded 05/09/2020
- ISRCTN14399966_Protocol.pdf
- Protocol file
Editorial Notes
06/11/2023: Protocol (not peer reviewed) added.
10/02/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
07/09/2020: Internal review.
04/09/2020: The participant information sheets have been uploaded as additional files.
02/09/2020: Trial’s existence confirmed by the Ethical Committee at the Faculty Hospital in Pilsen.
