Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01777126 |
| Other study ID # |
ONP |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
January 15, 2013 |
| Last updated |
July 16, 2014 |
| Start date |
January 2009 |
| Est. completion date |
November 2012 |
Study information
| Verified date |
January 2011 |
| Source |
Universitaire Ziekenhuizen Leuven |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Belgium: Ethics Committee |
| Study type |
Interventional
|
Clinical Trial Summary
After radical cystectomy, postoperative ileus (POI) is a common complication resulting in a
delayed oral nutritional intake with prolonged recovery and hospital stay. However, it is
questionable if nutritional support by routine use of parenteral nutrition (PN) is
justifiable.
A non-randomized before-after trial was conducted. Patients treated with an elective regular
radical cystectomy and without preoperative contra-indications for enteral nutrition were
eligible. In the control group, PN was initiated immediately after the procedure and
continued until resumption of diet. In the interventional group, an ONP was implemented. PN
could be initiated if oral intake was still insufficient after five days. The primary end
point was the postoperative length of stay.
Description:
Design
A prospective interventional non-randomized before-after trial was conducted. Eligible
patients admitted from 01/02/2009 were consecutively assigned to the control group until the
predefined sample size was reached. After enrollment and follow-up of control patients had
been finished, all newly admitted eligible patients were consecutively assigned to the
interventional group.
In addition to the before-after study, a sample of eligible patients was collected from
March 2011 to March 2013 (follow-up group) to examine the post-study impact of the ONP.
Patients
All adult patients admitted to the 48-bed urological ward in the 1850 bed University
Hospitals Leuven and treated with elective and regular RC, whether or not for underlying
cancer, were eligible for inclusion. Three different diversions are performed: an ileal
conduit, an orthothopic neobladder (N-pouch)12 or a continent cutaneous diversion. The
surgical procedure was considered regular if the patient returned after the procedure to the
urological ward and was not transferred to the intensive care unit. If the latter was deemed
necessary by the treating surgeon, the patient would be subjected to the intensive care
nutrition protocol. Therefore, only regular RC patients were included.
Exclusion criteria were transfer to the intensive care unit, preoperative contra-indications
for EN and discharge to a rehabilitation center. Contra-indications for EN were defined as
intestinal obstruction, malabsorption, multiple high-output fistula or intestinal ischemia8.
Uretero-ileal or ileo-ileal anastomoses, resulting from RC, were not considered as a
contra-indication for EN9,10. Discharge to a rehabilitation center could surpass one of the
criteria for discharge, i.e. the ability of independent mobilization, and could therefore
influence the postoperative LOS.
Care practices other than nutrition management
Preoperatively, all patients received bowel preparation with a 2 liter osmotic laxative
(macrogol 3350 100 g, sodiumsulphate 7.5 g, NaCl 2.69 g, KCl 1.02 g, sodium salt of ascorbic
acid 5.9 g and ascorbic acid 4.7 g). Before incision, a loading dose of 0.05 ml/cm epidural
analgesics (levobupivacaine 2,5 mg/ml and sufentanil 1 mcg/ml) was administered. During
surgery, a central venous catheter, a nasogastric or percutaneous gastrostomy tube and
ureteral stents were inserted. The nasogastric or percutaneous gastrostomy tube was removed
on the first or second postoperative day after restoration of transit (defined as a residual
gastric volume of less than 50 ml/24h). Acetaminophen, non-steroidal anti-inflammatory drugs
and patient-controlled epidural analgesia (PCEA; levobupivacaine 2,5 mg/ml and sufentanil 1
mcg/ml) were available for postoperative acute pain management. Intraoperative antimicrobial
prophylaxis consisted of cefazoline and metronidazole. Thromboprophylaxis consisted of
enoxaparin. Anti-emetics and other prokinetic drugs were not routinely administered but only
prescribed when needed. All treating surgeons were fully trained at the start of the study.
After a minimum of 10 days, ureteral stents were removed if the following 3 criteria were
met: restoration of transit, presence of bowel movements and absence of fever (defined as
body temperature <38,3 °C). Prophylactic levofloxacin 500 mg once daily was administered
after stent removal, until the first consultation. Patients were discharged if the following
4 criteria were fulfilled: 1) removal of all drains and stents, 2) the absence of fever
(body temperature < 38,3 °C), 3) the ability to tolerate solid food and 4) the ability of
independent mobilization.
The abovementioned care practices (anesthesia modalities, surgical techniques, doses of
narcotics, bowel stimulants and anti-nauseants, and mobilization practices) did not alter
during the course of the study.
Nutrition management
In the control group, PN was initiated immediately after surgery and continued until the
patient was able to tolerate solid food. PN infusion therapy consisted of Olimel® (Baxter
S.A., Lessines, Belgium) N7E 1000 ml, 1500 ml or 2000 ml; a parenteral solution with a total
energy of 1100 kcal/1000 ml and containing polyamino-acids (43.75g/1000 ml), glucose
(140g/1000ml), lipids (40g/1000ml) and electrolytes. Cernevit® (Baxter S.A., Lessines,
Belgium), a multivitamin powder for injection, and Addamel® (Fresenius Kabi, Schelle,
Belgium), a concentrate for injection containing trace elements, were added daily to the PN.
The amount of PN administered depended on the non-protein requirements, calculated by 30 ±
10% kcal/kg ideal body weight13. Extra fluids, up to two liter per day, were given
intravenously, at the discretion of the treating physician.
In the interventional group, the ONP was implemented (Table 1). Oral intake was increased
progressively with oral fluids and easily digestible food, independent of bowel movements.
The corresponding energy content from the meals and oral fluids were calculated. Fortimel
Jucy®, 200 ml containing 300 kcal, was used as the formulary energy sip. Extra fluids, up to
two liter per day, were given intravenously, at the discretion of the treating physician.
Nurses verified daily whether the patient was able to tolerate the ONP. If the patient
tolerated the ONP well, the oral intake was considered equal in terms of calories as the
corresponding oral meal in the ONP. From the sixth day, the patient was allowed to eat at
will. Only if oral intake remained insufficient after 5 days, which was left to the opinion
of the treating physician, PN could be initiated in this group.
Data collection
The following baseline demographic data were retrieved from medical files: patient
characteristics (gender, age, weight, length, body mass index, age-adjusted Charlson
comorbidity index14, indication for RC (oncologic or neurogenic) and bladder cancer staging
(TNM classification15)), surgical aspects (type of urinary diversion, attending surgeon,
intra-operative blood loss and duration of procedure), postoperative ileus (POI) and day of
nasogastric tube removal. The age-adjusted Charlson comorbidity index is a method for
classifying comorbid conditions. As the increase in elderly population and concurrent
increase in oncologic disease (and thus in bladder cancer) emphasized the importance of
understanding the interaction between age an comorbid illness on life expectancy, the age
-adjusted version was used. POI was defined as the inability to tolerate solid food, the
need to place a nasogastric tube in suction, the need to stop oral intake due to abdominal
distention (evaluated by the treating clinician), nausea or emesis.
Endpoints
The primary endpoint was LOS from surgery to discharge.
Secondary endpoints were the number of patients with successful implementation of the ONP,
as well as number of administered PN infusion bags per patient, time to resumption of full
diet, number of patients with one or more postoperative complications (POC), number of POCs
per patient, type and severity grade of POCs and the incidence of catheter related
bloodstream infections (CRBSIs). The implementation of the ONP was considered successful if
the protocol could be completely applied and no PN was needed. The type and severity of POCs
were classified using the Clavien-Dindo classification16. POCs were classified into 11
categories and stratified by severity. CRBSI, a common PN-related complication6, was defined
as bacteremia or fungemia in a patient having an intravascular device and more than one
positive blood culture result obtained from a peripheral vein, clinical manifestations of
infection (e.g., fever, chills, and/or hypotension) and no apparent other source for blood
stream infection17.
Post-study impact
An additional patient cohort was assembled, using the same inclusion and exclusion criteria
as described above. The LOS and number of PN infusion bags after surgery were determined and
compared to the results obtained from the intervention group.
Analysis of PN associated costs
The avoided PN cost per patient were calculated. For every group, the total number of PN
infusion bags was divided by the number of patients and multiplied by € 60, which was the
average actual cost in euros of one bag of Olimel® in Belgium at the time of the study. This
resulted in a direct and comparable PN infusion bag related cost per patient per group.
Statistical analysis and sample size calculation
Statistical analysis was performed by L-Biostat, Catholic University Leuven, using SPSS
package (SPSS Statistics 20.0 for Windows). Chi-square and Fisher's Exact tests were used
for categorical data. The unpaired T-test or the Wilcoxon rank sum test was used for normal
and non-normal distributed continuous variables respectively. Baseline demographic data and
the outcome measures were considered statistically significant if p-values were < 0.05. The
Bonferroni correction was used to account for multiple comparisons (6 secondary outcome
measures). Therefore, secondary outcome parameters were considered statistically significant
if p-values were < 0.008. To asses factors influencing LOS, general linear model statistics
- univariate analysis followed by ANOVA - were carried out.
Preliminary data from our institution showed that all RC patients receiving PN directly
after surgery were discharged after a mean of 19.3 ± 5.6 days. We expected to reduce our LOS
with 3 days from 19 to 16 days by implementing the ONP. Assuming that variances for both
groups are comparable, 88 (2x44) patients were needed, giving at least 80 % power (α=0.05,
one-tailed) to reject the null hypothesis defined as no difference in postoperative LOS
between the two groups.
The study was approved by the hospital's Ethics Committee and registered on clinical
trials.gov n° NCT01777126. No informed consent was obtained as the introduction of the ONP
was part of continuous improvement of standard of care in our hospital.
