The Enteral Resuscitation In Intensive Care Pilot- Study

Study Overview
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Brief Summary
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The purpose of this pilot study is to overcome the limited evidence on enteral fluid administration in intensive care medicine and to generate data for further hypothesis generation in an exploratory setting. This trial is a prospective, multicenter, randomized, parallel group, open-label study to compare the current standard of practice, the intravenous fluid administration, with a more physiological approach, the enteral fluid administration, in critically ill patients.

Detailed Description
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Introduction: The effectiveness and safety of enteral fluid administration in critically ill patients remains unclear. Existing evidence regarding this topic is scarce, but suggests that enteral fluid administration is a safe route of administration. To our knowledge no randomized controlled trial has been conducted investigating this topic. Objectives: The aim of this pilot study is to gather evidence on the impact of enteral fluid replacement on clinical, laboratory and outcome parameters in intensive care patients in order to plan a subsequent larger randomized controlled trial. Clinical outcomes indices evaluated are regurgitation, thirst, serum sodium, mortality, length of mechanical ventilation arterial pressure, urinary volume, body weight, edema, intra-abdominal pressure), changes in bioimpedance spectroscopy-derived markers, fluid overload, renal function tests, liver function tests and SOFA-Scores. Methods: The trial is a prospective, multicenter, randomized, parallel group, open-label study. Patients are going to be recruited and randomized at 3 separate internal medicine intensive care units in Vienna, Austria. A total of 64 patients will be recruited and randomized to receive enteral fluid administration via nasogastric tube or intravenous administration only. Daily visits and evaluation of clinical and radiological fluid status is performed by the attending physician. Regular study visits with Bioimpedance spectroscopy measurements (BIS) to evaluate fluid status are going to be performed Results and conclusions: The ERI study will provide data on potential outcome parameters to plan a subsequent larger randomized control trial for patients receiving enteral fluid therapy in intensive care medicine. Ethics and dissemination: The trial is performed in accordance with the Declaration of Helsinki. It subscribes to the principles outlined in the most recent version of the International Conference on Harmonization on Good Clinical Practice. Approval was obtained from the ethics committee of the Medical University of Vienna (EK number 1790/2020). The study has also been registered in a public clinical trial database (EudraCT Identifier Number 2018-002447-29, clinicaltrialsregister.eu).

Official Title
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The Enteral Resuscitation In Intensive Care (ERI) Pilot- Study: Enteral Versus Intravenous Fluid Administration in the Treatment of Critically Ill Patients: a Randomized Controlled Pilot Trial

Conditions
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Electrolyte Imbalance, Volume Overload, Hyperosmolality

Intervention / Treatment
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* Drug: Enteral Dose Form
* Drug: Intravenous Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patient intubated within the last 72h Age >18 years Expected required fluid volume may not exceed 4 mL/kg/h (permanently, during at least 24 hours). Negative pregnancy test in female patients of childbearing potential Informed consent. For patients that are temporarily unable to consent a subsequent informed consent must be provided. Exclusion criteria: Evidence of severe gastrointestinal disease defined as Gastrointestinal Failure with > 3 symptoms (see below) or Lactate >3mmol/L when mesenterial ischemia is a probable cause Clinical signs of intra-abdominal hypertension and an increase of intra-abdominal pressure of >20 mmHg. Patients who cannot receive early enteral nutrition due to conditions such as prone positioning in consequence of conditions such as acute respiratory distress syndrome Pregnancy Abdominal surgery in the last 3 months (unless all involved physicians, study investigators and caretaking doctors agree that the surgical event does not constitute a limitation for enteral fluid administration) Postoperative patients with consecutive admission to ICU Extracorporeal Kidney-Replacement Therapy before intubation At the discretion of the Investigator Symptoms of Gastrointestinal Failure: Absent bowel sounds Bowel distension Vomiting/regurgitation volume >500 ml GI bleeding Diarrhoea (liquid stool >3 times a day) Distended stomach on ultrasound examination.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, explorative, multicenter, randomized, parallel group, open-label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Intravenous Fluid Arm<br>In Group 1 (Standard of practice/intravenous fluid group) no enteral administration of fluid other than enteral nutrition is going to be allowed. Intravenous fluid administration is going to be administered at the discretion of the physician in charge and Elomel isoton is going to be the fluid of choice. | Drug: Intravenous Infusion<br>* In this intervention arm, fluid substitution is primarily done via intravenous administration. The used substance for intravenous fluid administered is going to be Elomel isoton.<br>|
| Active Comparator: Enteral Fluid Arm<br>In Group 2 (Test practice/enteral fluid group) enteral fluid administration is going to be the primary mode of administration. Intravenous fluid administration can be performed by physicians at their own discretion. Primary enteral fluid administered is going to be tap water, intravenous fluid of choice is going to be Elomel isoton. | Drug: Enteral Dose Form<br>* In this intervention arm, fluid substitution is primarily done via enteral administration. The used substance for enteral fluid administered is going to be tap water. Intravenous fluid of choice is going to be Elomel isoton.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regurgitation | Incidence and extent of regurgitation via the stomach/jejunal probe | From the moment of intubation to extubation. | 
| Sodium/Osmolality | Differences of serum sodium and serum osmolality | From the moment of intubation to extubation. | 
| Thirst | Thirst on a zero to 10 numeric rating scale (NRS; worst = 10) | On the last study visit (day of extubation) | 
| Days on ventilation | Days on ventilation | From the moment of intubation to extubation. | 
| 30-day mortality | 30-day mortality | From the moment of intubation until 30 days after intubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney Failure | Incidence and extent of kidney failure as well as kidney function | From the moment of intubation to extubation. | 
| SOFA-Score | Differences of Sequential Organ Failure Assessment (SOFA) Scores of patients. This score includes PaO2 [mmHg], FiO2 [%], mechanical ventilation [Yes/No], Platelets [/µL], Glascow Coma Scale, Bilirubin [mg/dL], Mean arterial pressure OR administration of vasoactive agents required and creatinine [mg/dL]. The score ranges from 0=best to 24=worst. | From the moment of intubation to extubation | 
| BCM | Differences in fluid volume status including Bioimpedance spectroscopy measurements (BIS) using Body Composition Monitor (BCM) | From the moment of intubation to extubation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluid Therapy, Critical Care, Prospective Studies, Pilot Project