Clinical trial NCT02358512: Intermittent Versus Continuous Feeding in ICU Patients
Official title: A Phase 2 Pilot Physiological Randomised Clinical Trial to Investigate the Effect of Intermittent Versus Continuous Enteral Nutrition on Muscle Wasting in Critical Illness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intensive Care (ICU) Myopathy
Keywords: Intensive Care
Recovery of Function
Survivors
Outcome Assessment (Health Care)
Medical Economics
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University College, London
name: The Whittington Hospital NHS Trust
First posted: 2015-02-09
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether intermittent nasogastric enteral feeding, rather than conventional continuous enteral feeding, will preserve muscle mass in the critically ill (Primary end-point). Such maintenance may translate into improved outcomes including reduced length of intensive care unit (ICU) and/or hospital stay, as well as number of days on a ventilator. In addition, long-term improvements in health-related quality of life and physical activity levels may result in these ICU survivors once they are back in the community. Indeed, such benefits could translate into reductions in primary healthcare usage and its related costs (secondary end-points).

Detailed description: This is a Phase II pilot single-blinded randomized controlled trial to be conducted in two adult intensive care units. Technically, the patient will be blinded (by virtue of illness), and in any case knowledge of the feeding intervention they are receiving would not influence outcome. Scans will be taken by staff who could potentially be aware of treatment; keeping scanner personnel blinded would involve complex logistics to separate those randomising, scanning patients, and collecting data; however, the investigators don't think that the individuals taking the scans would introduce material bias. Importantly, all scans will be analysed by the same individual (based off-site) who will be blind to treatment status.

Within 24 hours of admission to ICU, patients recruited to the study will be randomised to either intermittent enteral feeding or continuous enteral feeding - both regimens delivering the same nutritional content over a 24 hour period. The intermittent feeding regimen will consist of six bolus feeds (one bolus every four hours) while the continuous feeding regimen consists of the total volume of feed administered over 24 hours. Feed volume in both groups will commence according to a standard 'usual practice' protocol so as not to delay feeding, but each patient will then have an individual regimen calculated by the dietician. Feeding will continue as either intermittent or continuous for the duration of the trial period as tolerated.

Ultrasound of the thigh (enabling derivation of the Rectus Femoris cross sectional area (RFCSA)) will be performed on Days 1,7,10 (or at discharge, if sooner), and at hospital discharge (if after Day 10), with blood and urine samples taken daily. The hospital discharge destination will be noted, and functional assessment will be determined prior to hospital discharge by two validated methods previously used in this patient cohort (6-Minute Walk Distance and Short Performance Battery Test). Patients' health-related quality of life (HRQOL) will be determined for the pre-morbid period and at 12 months post ICU-discharge using the Short Form-36 health survey; primary care costs since discharge will also be ascertained.

Eligibility criteria: Inclusion Criteria:

* Due to receive enteral nutrition via nasogastric tube as part of routine care; endotracheally intubated and mechanically ventilated; likely to remain intubated for 48 hours; likely to remain on the ICU for \>7 days; and to survive intensive care admission.

Exclusion Criteria:

* Pregnancy
* Active disseminated malignancy (diagnosed or suspected)
* Unilateral/bilateral lower limb amputees
* Single Organ Failure (SOFA score less than 2)
* Patients with a primary neuromyopathy
* Patients entered into trials of interventions which would affect muscle mass
* Patients assessed as requiring sole/supplemental parenteral nutrition or post-pyloric feeding
* Patients requiring extra-corporeal membrane oxygenation (ECMO)
* Patients not meeting nutritional requirements in 72 hours using a standard feeding schedule
* Patients requiring the use of high protein feed
* Admission to ICU within the previous 3 months
* Ward patients who have received artificial enteral tube feeding within this hospital admission

Primary outcomes:
measure: Rectus Femoris cross-sectional area
timeFrame: Change between Day 1 and Day 10
Secondary outcomes:
measure: Length of stay on ICU
timeFrame: Participants will be followed for the duration of ICU stay, an expected average of 2.5 weeks
measure: Length of hospital stay
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 4.5 weeks
measure: Discharge Location
timeFrame: At hospital discharge, an expected average of 4.5 weeks after admission
measure: Number of days on ventilator
timeFrame: Ventilator days during ICU stay, an expected average of 2.5 weeks
measure: 6 Minute Walk Distance and Short Performance Battery Test
timeFrame: At hospital discharge, an expected average of 4.5 weeks after admission
measure: Health-related quality of life
timeFrame: 12 months post-ICU discharge
measure: Number of General Practitioner (GP) and nurse consultations
timeFrame: 12 months post-ICU discharge
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Whittington Hospital NHS Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Nicholas Hart, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Puthucheary ZA, Hart N. Skeletal muscle mass and mortality - but what about functional outcome? Crit Care. 2014 Feb 17;18(1):110. doi: 10.1186/cc13729.
citation: Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Phadke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE. Acute skeletal muscle wasting in critical illness. JAMA. 2013 Oct 16;310(15):1591-600. doi: 10.1001/jama.2013.278481.
citation: McNelly AS, Bear DE, Connolly BA, Arbane G, Allum L, Tarbhai A, Cooper JA, Hopkins PA, Wise MP, Brealey D, Rooney K, Cupitt J, Carr B, Koelfat K, Damink SO, Atherton PJ, Hart N, Montgomery HE, Puthucheary ZA. Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness: A Phase 2 Clinical Trial. Chest. 2020 Jul;158(1):183-194. doi: 10.1016/j.chest.2020.03.045. Epub 2020 Apr 2.