Trial Outcomes & Findings for Study of Refeeding to Optimize iNpatient Gains (NCT NCT02488109)

Last Updated: 2021-06-24

Results Overview

Clinical remission was defined as the combination of percentage mBMI and EDE-Q score at 1, 3, 6, and 12 months. This is a dichotomous variable 1/0. If participants achieve both weight recovery (defined as =\>95% of median BMI for sex and age), AND psychological recovery (defined as within 1SD of community norms for EDE-Q) then they are assigned a "1" for achieving clinical remission. If both parameters not met then "0" for not remitted.

Recruitment status

COMPLETED

Study phase

Target enrollment

120 participants

Primary outcome timeframe

up to 12 months

Results posted on

2021-06-24

Participant Flow

Patients were enrolled from February 8, 2016, to March 7, 2019 at 2 clinical sites, large tertiary care children's hospitals with eating disorder inpatient programs attended by interdisciplinary adolescent medicine care teams at the University of California San Francisco and Stanford University. Written informed consent was obtained from young adults and parents of minors, who provided written assent.

Although 120 participants were randomized,116 started on the study. Of the 4 individuals who were randomized but did not receive treatment, 3 were found ineligible and 1 did not complete the consent, leaving 56 individuals in the LCR arm. Of those 56 individuals, an additional 5 individuals withdrew prior to receiving treatment, ultimately resulting in 51 participants in the LCR arm.

Participant milestones

Participant milestones
Measure	Higher Calorie Refeeding (HCR) Protocol Meal-based refeeding in hospital: starting 2000 kcal/d and increasing 200 kcal/d to goal	Lower Calorie Refeeding (LCR) Protocol Meal-based refeeding in hospital: starting 1400 kcal/d and increasing 200 kcal every other day to goal
Treatment in Hospital STARTED	60	56
Treatment in Hospital Received Treatment	60	51
Treatment in Hospital Included in mITT Analysis	60	51
Treatment in Hospital COMPLETED	60	51
Treatment in Hospital NOT COMPLETED	0	5
12-month Follow-Up STARTED	60	51
12-month Follow-Up Included in mITT Analysis	60	51
12-month Follow-Up COMPLETED	56	44
12-month Follow-Up NOT COMPLETED	4	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Higher Calorie Refeeding (HCR) Protocol Meal-based refeeding in hospital: starting 2000 kcal/d and increasing 200 kcal/d to goal	Lower Calorie Refeeding (LCR) Protocol Meal-based refeeding in hospital: starting 1400 kcal/d and increasing 200 kcal every other day to goal
Treatment in Hospital Withdrawal by Subject	0	5
12-month Follow-Up Lost to Follow-up	4	7

Baseline Characteristics

Study of Refeeding to Optimize iNpatient Gains

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Higher Calorie Refeeding (HCR) Protocol n=60 Participants Meal-based refeeding in hospital: starting 2000 kcal/d and increasing 200 kcal/d to goal	Lower Calorie Refeeding (LCR) Protocol n=56 Participants Meal-based refeeding in hospital: starting 1400 kcal/d and increasing 200 kcal every other day to goal	Total n=116 Participants Total of all reporting groups
Age, Continuous	16.6 years STANDARD_DEVIATION 2.5 • n=5 Participants	16.2 years STANDARD_DEVIATION 2.4 • n=7 Participants	16.4 years STANDARD_DEVIATION 2.5 • n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	52 Participants n=7 Participants	105 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · Non-Hispanic White	36 Participants n=5 Participants	33 Participants n=7 Participants	69 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · Asian	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · Hispanic or Latino	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized Race/ethnicity · Other or >1 race/ethnicity reported	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment United States	60 Participants n=5 Participants	56 Participants n=7 Participants	116 Participants n=5 Participants
Admission percentage of median body mass index (%mBMI)	83.3 % of mBMI STANDARD_DEVIATION 11.1 • n=5 Participants	86.6 % of mBMI STANDARD_DEVIATION 12.2 • n=7 Participants	84.6 % of mBMI STANDARD_DEVIATION 11.9 • n=5 Participants
Lowest 24-hr heart rate, beats/min	41.5 beats per minute STANDARD_DEVIATION 6.9 • n=5 Participants	40.7 beats per minute STANDARD_DEVIATION 5.9 • n=7 Participants	41.3 beats per minute STANDARD_DEVIATION 6.1 • n=5 Participants
Lowest Systolic Blood Pressure (mm Hg)	94.2 mm Hg STANDARD_DEVIATION 8.0 • n=5 Participants	93.3 mm Hg STANDARD_DEVIATION 8.3 • n=7 Participants	93.7 mm Hg STANDARD_DEVIATION 8.1 • n=5 Participants
Global Eating Disorder Examination Questionnaire score (mean, SD)	3.32 Score on a scale STANDARD_DEVIATION 1.68 • n=5 Participants	3.45 Score on a scale STANDARD_DEVIATION 1.71 • n=7 Participants	3.34 Score on a scale STANDARD_DEVIATION 1.70 • n=5 Participants
Atypical anorexia nervosa (No., %)	21 Participants n=5 Participants	27 Participants n=7 Participants	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 12 months

Population: Clinical remission defined as the combination of %mBMI and EDE-Q score. Instead of assuming missing data at random in the generalized linear mixed-effects regression model, clinical remission was modeled as a nominal multinomial outcome (yes, no, or missing), with time (1, 3, 6, or 12 months after discharge), treatment group, and time\*treatment group interaction as fixed effects. Longitudinal analysis included only participants with both %mBMI and EDE-Q scores.

Outcome measures

Outcome measures
Measure	Higher Calorie Refeeding (HCR) Protocol n=44 Participants Meal-based refeeding in hospital: starting 2000 kcal/d and increasing 200 kcal/d to goal	Lower Calorie Refeeding (LCR) Protocol n=34 Participants Meal-based refeeding in hospital: starting 1400 kcal/d and increasing 200 kcal every other day to goal
Number of Participants With Clinical Remission at Different Time Points of Assessment 1 month	12 Participants	8 Participants
Number of Participants With Clinical Remission at Different Time Points of Assessment 3 months	10 Participants	13 Participants
Number of Participants With Clinical Remission at Different Time Points of Assessment 6 months	16 Participants	10 Participants
Number of Participants With Clinical Remission at Different Time Points of Assessment 12 months	18 Participants	13 Participants

SECONDARY outcome

Timeframe: Inpatient hospitalization from day of admission to day of discharge, average of 10 days

Population: Modified intention to treat analysis (mITT) included all participants who received at least one day of treatment

Medical stability was adjudicated by a 6-point clinical index: (1) 24-hour heart rate of 45 beats/min or more, (2) systolic blood pressure of 90 mm Hg or more, (3) temperature of 35.6 °C or more, (4) orthostatic increase in heart rate of 35 beats/min or less, (5) orthostatic decrease in systolic blood pressure of 20 mm Hg or less, and (6) 75% or more of mBMI for age and sex. Criteria were assessed daily; for vital signs with multiple daily measures, the most deviant value was recorded (eg, lowest heart rate). Each criterion was scored as "1" if met, "0" if unmet, and missing (not scored) if not measured. Medical stability was considered restored when all measured criteria were stable for 24 hours, allowing a maximum of 2 missing values. Additional efficacy outcomes were time to restore heart rate to 45 beats/min or more (among those with bradycardia at baseline) and weight gain (change in percentage mBMI).

Outcome measures

Outcome measures
Measure	Higher Calorie Refeeding (HCR) Protocol n=60 Participants Meal-based refeeding in hospital: starting 2000 kcal/d and increasing 200 kcal/d to goal	Lower Calorie Refeeding (LCR) Protocol n=51 Participants Meal-based refeeding in hospital: starting 1400 kcal/d and increasing 200 kcal every other day to goal
Time to Achieve Medical Stability in Hospital	7.0 Days Standard Deviation 7.0	10.0 Days Standard Deviation 8.0

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 12 months

Population: The analysis was a modified intent-to-treat (mITT) approach including all randomized participants who received treatment for at least one day. A total of 9 participants were excluded: 3 were found to be ineligible after randomization and 6 withdrew prior to receiving treatment.

defined as total cost (direct and indirect costs)

Outcome measures

Outcome measures
Measure	Higher Calorie Refeeding (HCR) Protocol n=60 Participants Meal-based refeeding in hospital: starting 2000 kcal/d and increasing 200 kcal/d to goal	Lower Calorie Refeeding (LCR) Protocol n=51 Participants Meal-based refeeding in hospital: starting 1400 kcal/d and increasing 200 kcal every other day to goal
Cost-effectiveness Per Adolescent Recovered	38,112 USD Standard Deviation 26,043	57,168 USD Standard Deviation 30,486

Adverse Events

Higher Calorie Refeeding (HCR)

Serious events: 14 serious events

Other events: 14 other events

Deaths: 0 deaths

Lower Calorie Refeeding (LCR)

Serious events: 10 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Higher Calorie Refeeding (HCR) n=60 participants at risk Meal-based refeeding in hospital: starting 2000 kcal/d and increasing 200 kcal/d to goal	Lower Calorie Refeeding (LCR) n=51 participants at risk Meal-based refeeding in hospital: starting 1400 kcal/d and increasing 200 kcal every other day to goal. Of the 56 participants originally randomized to this treatment, 5 never received treatment and were therefore excluded from mITT analyses.
Metabolism and nutrition disorders Hypophosphatemia	1.7% 1/60 • Number of events 1 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.	2.0% 1/51 • Number of events 1 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.
Metabolism and nutrition disorders Orthostatic increase in heart rate	6.7% 4/60 • Number of events 20 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.	7.8% 4/51 • Number of events 16 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.
Psychiatric disorders Psychiatric SAE, e.g. suicide attempt	5.0% 3/60 • Number of events 4 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.	5.9% 3/51 • Number of events 3 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.
Metabolism and nutrition disorders Severe Bradycardia	0.00% 0/60 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.	2.0% 1/51 • Number of events 1 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.
Metabolism and nutrition disorders Severe Hypotension	0.00% 0/60 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.	2.0% 1/51 • Number of events 1 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.
Metabolism and nutrition disorders Other unrelated SAEs during follow-up period	10.0% 6/60 • Number of events 6 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.	0.00% 0/51 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.

Other adverse events

Other adverse events
Measure	Higher Calorie Refeeding (HCR) n=60 participants at risk Meal-based refeeding in hospital: starting 2000 kcal/d and increasing 200 kcal/d to goal	Lower Calorie Refeeding (LCR) n=51 participants at risk Meal-based refeeding in hospital: starting 1400 kcal/d and increasing 200 kcal every other day to goal. Of the 56 participants originally randomized to this treatment, 5 never received treatment and were therefore excluded from mITT analyses.
Metabolism and nutrition disorders Hypokalemia (mild)	5.0% 3/60 • Number of events 4 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.	9.8% 5/51 • Number of events 5 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.
Metabolism and nutrition disorders Hypomagnesemia (mild)	11.7% 7/60 • Number of events 10 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.	27.5% 14/51 • Number of events 16 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.
Metabolism and nutrition disorders Hypophosphatemia (moderate)	6.7% 4/60 • Number of events 4 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.	3.9% 2/51 • Number of events 2 • Participants were monitored for adverse events on an ongoing basis during the treatment period, which was during hospitalization from day of admission to day of discharge (an average of 10 days). After the treatment effect window was completed on discharge from the hospital, adverse events were not considered to be related to study treatment.

Additional Information

Andrea Garber, PhD, RD

University of California, San Francisco, Department of Pediatrics

Phone: 415-514-2180

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place