Clinical trial NCT02517476: Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial
Official title: Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial: The EFFORT Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malnutrition
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: Insel Gruppe AG, University Hospital Bern
name: Luzerner Kantonsspital
name: Kantonsspital Münsterlingen
name: Clinical Trial Unit, University Hospital Basel, Switzerland
First posted: 2015-08-07
Enrollment: 2088
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aims of the randomized-controlled, multicenter EFFORT trial are to assess the effects of early nutritional therapy in regard to effectiveness, safety and costs when applied to the heterogenous, polymorbid medical inpatient population. EFFORT will not only answer the question about overall benefit or harm, but using a physio-pathological mechanistic approach, it also will explore and provide conclusive answers about whether, why, how, and in which patient populations nutritional therapy does and does not works.

Detailed description: The aims of the randomized-controlled, multicenter EFFORT trial are to test the hypothesis that in medical inpatients at risk for undernutrition defined by the nutritional risk score (NRS 2002), early tailored nutritional therapy to reach nutritional targets based on individualized nutritional counseling is a cost-effective strategy to prevent mortality, morbidity and functional decline.

The primary composite endpoint is combined adverse outcome within 30 days defined as (a) all-cause mortality, (b) admission to the intensive care unit from the medical ward, (c) major complications, (d) unplanned hospital readmissions and (d) decline in functional outcome from admission to day 30 assessed by Barthel's index (-10%). Secondary endpoints include (a) each single component of the primary endpoint (b) short-term nutritional and functional outcomes from inclusion to day 10 or hospital discharge; (c) hospital outcomes; (d) 30-day and 180-day outcomes (e) Other safety endpoints including adverse gastrointestinal effects associated with nutritional therapy assessed daily until hospital discharge.

The investigators will include unselected adult medical inpatients at risk of undernutrition \[NRS≥3 points\] and an expected hospital stay of ≥5 days who are willing to provide informed consent. The investigators will exclude patients in critical care or post-operative state, unable to swallow, at long-term need for parenteral/enteral nutrition, in terminal condition, pregnant, with acute pancreatitis or acute liver failure, with anorexia nervosa, that were earlier included into the trial Patients in the intervention group will receive individualized nutritional therapy to reach nutritional targets (caloric, protein, micronutrients, other) based on a predefined nutritional strategy. In control patients, according to patients' appetite, standard hospital nutrition will be served. Nutritional therapy may be started in control patients, if any sort of swallowing disorders develops or if patients need to be prepared for operation. All patients will be re-assessed daily during the hospital stay for nutritional intake and nutritional therapy may be escalated every 24-48 hours (food fortification, oral supplements, enteral, parenteral nutrition) if targets are not met (at least 75% of targets).

The targeted sample size is 2000 - 3000 patients. The inclusion of 2000 - 3000 patients will provide between 76% and 91% power to detect a reduction in the primary endpoint of 15% (from 40% to 34%) assuming a lost to follow up rate of 10%.

Eligibility criteria: Inclusion criteria:

* NRS ≥3 points
* expected hospital LOS ≥5 days (as estimated by the treating physician team)
* willingness to provide informed consent (see informed consent statement)

Exclusion criteria

* initially admitted to critical care units (except intermediate care)
* scheduled for surgery or in an immediate post-operative state
* unable to ingest oral nutrition and thus need for enteral or parenteral nutrition
* admitted with, or scheduled for, total parenteral nutrition or tube feeding
* currently under nutritional therapy (defined by at least one visit with a dietician in the last month)
* who are hospitalized because of anorexia nervosa
* in terminal condition (end of life situation)
* hospitalized due to acute pancreatitis
* hospitalized due to acute liver failure
* earlier inclusion into this trial
* cystic fibrosis
* patients after gastric bypass operations
* stem cell transplantation
* any contraindication against nutritional therapy (i.e., enteral and/or parenteral)

Primary outcomes:
measure: primary composite endpoint
timeFrame: measured at day 30 by telephone interview
Secondary outcomes:
measure: Weight change
timeFrame: measured at day 30 by telephone interview
measure: lenght of hospital stay
timeFrame: participants will be followed for the duration of hospital stay with an expected average of 10 days
measure: Improvement in quality of life
timeFrame: measured at days 30 and 180 by telephone interview
measure: Combined safety endpoints in regard to side effects from nutritional therapy
timeFrame: measured at day 30
measure: new decubital ulcer
timeFrame: assessed on the day of hospital discharge after an expected average of 10 days
measure: Discharge location
timeFrame: assessed on the day of hospital discharge after an expected average of 10 days
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: University Clinic, Kantonsspital Aarau
state: AG
Study officials:
affiliation: University Clinic, Kantonsspital Aarau
name: Philipp Schuetz, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schuetz P. "Eat your lunch!" - controversies in the nutrition of the acutely, non-critically ill medical inpatient. Swiss Med Wkly. 2015 Apr 23;145:w14132. doi: 10.4414/smw.2015.14132. eCollection 2015.
citation: Schutz P, Bally M, Stanga Z, Keller U. Loss of appetite in acutely ill medical inpatients: physiological response or therapeutic target? Swiss Med Wkly. 2014 Apr 29;144:w13957. doi: 10.4414/smw.2014.13957. eCollection 2014.
citation: Stalder L, Kaegi-Braun N, Gressies C, Gregoriano C, Tribolet P, Lobo DN, Gomes F, Hoess C, Pavlicek V, Bilz S, Sigrist S, Brandle M, Henzen C, Thomann R, Rutishauser J, Aujesky D, Rodondi N, Donze J, Stanga Z, Mueller B, Schuetz P. Prospective validation of five malnutrition screening and assessment instruments among medical inpatients: Secondary analysis of a randomized clinical trial. Clin Nutr. 2022 Jun;41(6):1307-1315. doi: 10.1016/j.clnu.2022.04.025. Epub 2022 Apr 26.
citation: Struja T, Laczko E, Wolski W, Schlapbach R, Mueller B, Roschitzki B, Schuetz P. Association of proteomic markers with nutritional risk and response to nutritional support: A secondary pilot study of the EFFORT trial using an untargeted proteomics approach. Clin Nutr ESPEN. 2022 Apr;48:282-290. doi: 10.1016/j.clnesp.2022.01.035. Epub 2022 Feb 2.
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citation: Schuetz P, Sulo S, Walzer S, Vollmer L, Stanga Z, Gomes F, Rueda R, Mueller B, Partridge J; EFFORT trial collaborators. Economic evaluation of individualized nutritional support in medical inpatients: Secondary analysis of the EFFORT trial. Clin Nutr. 2020 Nov;39(11):3361-3368. doi: 10.1016/j.clnu.2020.02.023. Epub 2020 Feb 25.
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