Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial

Study Overview
=================
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%.

Official Title
-----------------
Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial: The EFFORT Trial

Conditions
-----------------
Malnutrition

Intervention / Treatment
-----------------
* Dietary Supplement: Nutritional therapy


Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nutritional support<br>For the purpose of this study, we have developed nutritional guidelines by consensus and adapted to current guidelines (e.g., ESPEN, ASPEN). These guidelines specify a reinforced nutritional therapy strategy to cover nutritional requirements, focusing on nutritional targets based on the specific nutritional diagnoses defined by the IDNT. The nutritional guidelines may vary according to important medical diagnoses (i.e. renal failure). They specify not only nutritional targets, but also escalation of the route (i.e. food fortification, oral, enteral, parenteral) if targets cannot be achieved (≤75%) every 5 hours. Nutritional goals are being assessed daily in patients in the intervention group. | Dietary Supplement: Nutritional therapy<br>* Any nutritional product and route (i.e. food fortification, oral, enteral, parenteral) is possible to reach goals<br>|
| No Intervention: Usual care (appetite-guided) controls<br>In control patients, we will use conventional nutrition according to the ability and desire of the patient to eat, using standard care food provided by the hospital kitchen (appetite-guided). | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| primary composite endpoint | Number of participants with adverse events including All-cause mortality Admission to the intensive care unit Unplanned hospital readmission after hospital discharge Major complications including nosocomial infection or abscess requiring antibiotic treatment, respiratory failure with need for invasive or non-invasive ventilation, major cardiovascular event or pulmonary embolism, acute renal failure (defined by 2x increase of baseline creatinine or new requirement of dialysis), gastro-intestinal hemorrhage or intestinal perforation assessed by medical chart review and telephone interview decline in functional status of 10% or more from admission to day 30 measured by the Barthel's index assessed by patient interview on admission and after 30 days | measured at day 30 by telephone interview | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight change | change in weight and BMI from inclusion to day 30 by patient interview and medical chart review | measured at day 30 by telephone interview | 
| lenght of hospital stay | days in the hospital within index hospitalisation and within the 30 days of follow up measured by patient interview and medical chart review | participants will be followed for the duration of hospital stay with an expected average of 10 days | 
| Improvement in quality of life | Improvement in quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire on admission and during follow up measured by patient interview | measured at days 30 and 180 by telephone interview | 
| Combined safety endpoints in regard to side effects from nutritional therapy | Number of participants with side effects from nutritional therapy including (a) adverse gastrointestinal effects (diarrhea, nausea, vomiting, abdominal pain) assessed by patient interview (yes/no) b) Complications due to tube feeding or center catheter for parenteral nutrition assessed by medical chart review (c) Refeeding syndrome assessed by chart review (d) Acute pancreatitis defined as 2 out of 3 criteria: abdominal pain, 3-fold increase in lipase or amylase, characteristic imaging findings assessed by chart review (e) Liver or gall bladder dysfunction assessed by chart review (f) Hyperglycemia (defined as glucose levels >12mmol/l or persistent levels >10mmol/l in patients without diabetes or well controlled diabetes) assessed by medical chart review | measured at day 30 | 
| new decubital ulcer | Clinical diagnosis of decubital ulcer with onset after study inclusion measured by patient interview and medical chart review | assessed on the day of hospital discharge after an expected average of 10 days | 
| Discharge location | proportion discharge home or to a rehab facility measured by patient interview and medical chart review | assessed on the day of hospital discharge after an expected average of 10 days |