ONC: Hematopoietic Cell Transplant (2006)

Citation:

Charuhas PM, Fosberg KL, Bruemmer B, Aker SN, Leisenring W, Seidel K, Sullivan KM.A double-blind randomized trial comparing outpatient parenteral nutrition with intravenous hydration: effect on resumption of oral intake after marrow transplantation. JPEN J Parenter Enteral Nutr. 1997 May-Jun;21(3):157-61.

PubMed ID: 9168368

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To evaluate the effect of parenteral nutrition (PN) on time to resumption of oral intake and medical outcome in patients undergoing marrow transplant.

Inclusion Criteria:

Patients that marrow transplant
Oral intake <70% caloric requirements at time of hospital discharge
Age >= 2 years
Discharge before day 65 post-transplant
Insulin requirement of <= 10 units
Tolerance of at least GVHD- II (low lactose, low fiber, low fat) oral diet

Exclusion Criteria:

Not Specified

Description of Study Protocol:

Recruitment Not specified

Design `Subjects were stratified by age (<12 years vs. >= 12 years) and corticosteroid administration at time of randomization. Patients were randomized to receive one of the following:

Parenteral Nutrition (PN) comprised of 25% dextrose and 5% amino acid (4.25% in peds)
IV (IVF) hydration fluid consisting of 5% dextrose

Both groups received daily oral MVI and trace element supplements. Fluid volumes were based on weight (< 20kg:<= 1000ml/d; 20-35kg: <=1500ml/d; 35-70kg: <=2000ml/d; >=70kg: <=2500ml/d)

Inital IV supplementation was calculate to supplement oral intake to provide at least 100% of the patient's estimated energy requirement (EER) as estimated by Harris Benedict (130% for adults, 140% for children). Patients and staff were blinded to the treatment assignment.

Subjects visited the study dietitian once a week, weights were taken 4 days later. Daily food and fluid records were kept by patients and reviewed by the dietitian every 3 days. The volume of the IV supplementation was adjusted according to the food records based on the following schedule:

Patients >35kg
- Sum of intake (PO + IV) > EER by 300 kcal for 3 days: Volume of study soultion decreased by 500ml
- Sum of intake (PO + IV) < EER by 300 kcal for 3 days: Volume of study soultion increased by 500ml
Patients <=35kg
- Sum of intake (PO+IV) > EER by 150 Kcal for 3 days: Volume of study solution decreased by 250ml
- Sum of intake (PO+IV) < EER by 150 Kcal for 3 days: Volume of study solution increased by 250ml

Subjects were removed from the sudy in the following cases:

Successful refeeding
- Oral intake >= 85% of EER for 3 consecutive days
Weight loss
- Adults: <= 80% IBW or hospital admission weight
- Children: <=90% IBW or hospital admission weight
- Required hospital re-admission

Blinding used (if applicable) Patients and researchers were blinded to the study assignment. Only the study pharmacist knew the assignment. Solutions were prepared to appear identical.

Intervention (if applicable) Patients were randomized to receive one of the following:

Parenteral Nutrition (PN) comprised of 25% dextrose and 5% amino acid (4.25% in peds)
IV (IVF) hydration fluid consisting of 5% dextrose

Both groups received daily oral MVI and trace element supplements. Fluid volumes were based on weight (< 20kg:<= 1000ml/d; 20-35kg: <=1500ml/d; 35-70kg: <=2000ml/d; >=70kg: <=2500ml/d). The volume of the IV supplementation was adjusted according to the food records based on the following schedule:

Patients >35kg
- Sum of intake (PO + IV) > EER by 300 kcal for 3 days: Volume of study soultion decreased by 500ml
- Sum of intake (PO + IV) < EER by 300 kcal for 3 days: Volume of study soultion increased by 500ml
Patients <=35kg
- Sum of intake (PO+IV) > EER by 150 Kcal for 3 days: Volume of study solution decreased by 250ml
- Sum of intake (PO+IV) < EER by 150 Kcal for 3 days: Volume of study solution increased by 250ml

Patients successfully completed the study when oral consumption reached >=85% EER.

Statistical Analysis The following statistical tests were used:

Multivariate modeling
Log-rank test
Kaplan Meier Plots
Cox Regression analysis
Wilcoxon Rank Sum
ANOVA
Pearson Chi Square
Significance <=0.049

Data Collection Summary:

Timing of Measurements Measurements were taken according to the following schedule:

Daily Food Diary: Daily through day 28
Daily Fluid Diary: Daily through day 28
Nutrition Analysis: Three times a week
Weight: Weekly

Dependent Variables

Variable 1: Time to resumption of oral intake as measured in days and defined by oral consumption of >=85% of needs for 3 consecutive days
Variable 2: Hospital readmission rates
Variable 3: Percentage weight change from pre-transplant to end of study
Variable 4: Relapse and survival as measured to day 150 post-transplant

Independent Variables Provision of PN (carbohydrate and protein) was examined as independent.

Description of Actual Data Sample:

Initial N: 258

PN: 128(69 males, 59 females)
IVF: 130(70 males, 60 females)

Attrition (final N): 249

Age:

Age (Years)	PN (n=128)	IVF (n=130)
< 10 years	14	14
10-20 years	16	13
20-30 years	52	60
>40 years	46	43

Ethnicity: Not Specified

Other relevant demographics:

Donor Type	PN (n=128)	IVF (n=130)
Autologous	30	23
Syngeneic	3	2
Allogeneic
HLA-compatible related donor	67	70
Unrelated donor	35	35

Diagnosis	PN (n=128)	IVF (n=130)
Aplastic anemia	0	2
Acute lymphoblastic leukemia	18	14
Acute nonlymphoblastic leukemia	28	21
Chronic myelogenous leukemia	46	58
Congenital disorders	1	2
Hodgkin’s disease	2	3
Myelodysplastic syndrome	4	9
Multiple myeloma	6	4
Non-Hodgkin’s lymphoma	17	11
Solid tumors	6	6

Anthropometrics Initial anthropometrics not described

Location: Fred Hutchinson Cancer Center and the Swedish Medical Center.

Summary of Results:

Median time to resumption of oral intake:
- IVF: 10 days
- PN: 16 days
- p = 0.049
1.47 Relative risk of longer need for supplementation in PN group (p=0.038)
IVF group resumed oral intake sooner than PN group (RR=1.51; 95%CI 1.04 to 2.19; p=0.029)
- Fluid volume did not alter association

Percent Weight Change Pretransplant to Day 28

Weeks of PN	PN	IVF	p-Value
0-1	1.98 ± 0.95	0.14 ± 0.82	NS
1-2	2.08 ± 1.51	-0.91 ± 1.08	NS
2-3	-0.20 ± 0.93	-1.58 ± 2.44	NS
3-4	-1.56 ± 1.43	-3.84 ± 0.91	NS
Total	0.87 ± 0.61	-0.23 ± 0.58	p=0.026

Percent Weight Change Pretransplant to Discharge Home

Weeks of PN	PN	IVF	p-Value
0-1	3.26 ± 1.30	0.19 ± 1.07	NS
1-2	0.62 ± 1.87	-2.15 ± 1.02	NS
2-3	0.50 ± 2.10	-2.89 ± 2.75	NS
3-4	-1.27 ± 1.84	-4.63 ± 1.05	NS
Total	1.41 ± 0.86	-1.14 ± 0.71	p=0.004

Patients in the IVF group lost significantly more weight by discharge home (p=0.026)
- Significance persisted (p=0.004) despite controlling for sex, age, donor type, acute GVHD, total body irradiation, prednisone therapy, time of posttransplant randomization

Patient Outcomes

	PN	IVF	p-Value
Readmission while on study
Yes	46	40	NS
No	82	90	NS
Disease relapse before day 150
Yes	22	23	NS
No	106	107	NS
Death before day 150
Yes	27	26	NS
No	101	104	NS

Other Findings:

Cost of Supplementation
- IVF: $300 (2L/day for 10 days)
- PN: $4,160 (2L/day for 16 days)

Author Conclusion:

Outpatient parenteral nutrition delays resumption of oral intake. Intravenous hydration fluid (5% dextrose) does not produce adverse outcomes. Parenteral nutrition should be reserved for transplant patients with severe gastrointestinal dysfunction.

Funding Source:

University/Hospital:

Jagiellonian University College of Medicine

Reviewer Comments:

This well planned study indicated that there is no benefit in the provision of PN to marrow transplant patients able to consume at least 70% or estimated energy requirements. The following information limits the results:

Exclusion criteria not specified
No description of ethnicity
No description of baseline anthropometrics
No description of attrition and if it was simialr in both groups
No description of the facility
No description relating to randomization
Tables do not add up to total "n"

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
	3.	Were study groups comparable?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
	4.	Was method of handling withdrawals described?	No
4.	Was method of handling withdrawals described?		No
	4.1.	Were follow-up methods described and the same for all groups?	No
	4.1.	Were follow-up methods described and the same for all groups?	No
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	No
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	5.	Was blinding used to prevent introduction of bias?	Yes
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
	6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?	Yes
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
	7.	Were outcomes clearly defined and the measurements valid and reliable?	Yes
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
	8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	No
	8.6.	Was clinical significance as well as statistical significance reported?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
	9.	Are conclusions supported by results with biases and limitations taken into consideration?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
	9.2.	Are biases and study limitations identified and discussed?	No
	10.	Is bias due to study's funding or sponsorship unlikely?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes