Trial Outcomes & Findings for Oral Nutrition After Regular Radical Cystectomy (NCT NCT01777126)

NCT ID: NCT01777126

Last Updated: 2014-07-17

Results Overview

The primary outcome measure was the interval from surgery to discharge. Discharge means that the patient returns to his home.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 94 participants
• Primary outcome timeframe: one month after surgery
• Results posted on: 2014-07-17

Participant Flow

All adult patients admitted undergoing an elective and unproblematic radical cystectomystarting in 01/02/2009 were consecutively assigned to the control group until the predefined sample size was attained. After completion of the control group, all newly admitted patients were, again consecutively, assigned to the experimental group.

If a transfer was needed, the patient was excluded. Other exclusion criteria were preoperative contra-indications for EN and discharge to a rehabilitation center.

Participant milestones

Measure	Control Group In the control group, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group In this group, oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
Overall Study STARTED	48	46
Overall Study COMPLETED	48	46
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Oral Nutrition After Regular Radical Cystectomy

Baseline characteristics by cohort

Measure	Control Group n=48 Participants Subjects enrolled in this arm will undergo the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group n=46 Participants Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.	Total n=94 Participants Total of all reporting groups
Age, Continuous Age	66.0 years INTER_QUARTILE_RANGE 12.5 • n=5 Participants	65.5 years INTER_QUARTILE_RANGE 10.8 • n=7 Participants	66 years INTER_QUARTILE_RANGE 11.6 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	12 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	34 Participants n=7 Participants	65 Participants n=5 Participants
Length	169.7 cm STANDARD_DEVIATION 8.2 • n=5 Participants	170.8 cm STANDARD_DEVIATION 8.0 • n=7 Participants	170.3 cm STANDARD_DEVIATION 8.1 • n=5 Participants
Weight	73.7 kg STANDARD_DEVIATION 13.9 • n=5 Participants	75.4 kg STANDARD_DEVIATION 14.2 • n=7 Participants	74.6 kg STANDARD_DEVIATION 14.1 • n=5 Participants
Body Mass Index	25.5 kg/m² STANDARD_DEVIATION 4.0 • n=5 Participants	25.8 kg/m² STANDARD_DEVIATION 4.3 • n=7 Participants	25.7 kg/m² STANDARD_DEVIATION 4.1 • n=5 Participants
Age-adjusted Charlson Comorbidity Index	4 Points INTER_QUARTILE_RANGE 1.7 • n=5 Participants	5 Points INTER_QUARTILE_RANGE 2.6 • n=7 Participants	4 Points INTER_QUARTILE_RANGE 2.3 • n=5 Participants
Indication Neurogenic	9 participants n=5 Participants	6 participants n=7 Participants	15 participants n=5 Participants
Indication Oncologic	39 participants n=5 Participants	40 participants n=7 Participants	79 participants n=5 Participants
Bladder staging T+N0M0	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Bladder staging T+N+M0	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Bladder staging T+N+M+	38 participants n=5 Participants	40 participants n=7 Participants	78 participants n=5 Participants
Bladder staging T0N0M0	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants
Type of urinary diversion Ileal conduit	40 participants n=5 Participants	39 participants n=7 Participants	79 participants n=5 Participants
Type of urinary diversion Orthothopic neobladder	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants
Type of urinary diversion Continent cutaneous diversion	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Surgeon Surgeon 1.	5 participants n=5 Participants	0 participants n=7 Participants	5 participants n=5 Participants
Surgeon Surgeon 2.	19 participants n=5 Participants	14 participants n=7 Participants	33 participants n=5 Participants
Surgeon Surgeon 3.	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Surgeon Surgeon 4.	19 participants n=5 Participants	29 participants n=7 Participants	48 participants n=5 Participants
Blood loss	1000 ml INTER_QUARTILE_RANGE 600 • n=5 Participants	1000 ml INTER_QUARTILE_RANGE 589 • n=7 Participants	1000 ml INTER_QUARTILE_RANGE 595 • n=5 Participants
Duration of procedure	210 minute INTER_QUARTILE_RANGE 55.4 • n=5 Participants	187.5 minute INTER_QUARTILE_RANGE 46.8 • n=7 Participants	210 minute INTER_QUARTILE_RANGE 51.1 • n=5 Participants
Postoperative ileus POI	9 participants n=5 Participants	13 participants n=7 Participants	22 participants n=5 Participants
Postoperative ileus no POI	39 participants n=5 Participants	33 participants n=7 Participants	72 participants n=5 Participants
Nasogastric tube removal day	2 day n=5 Participants	2 day n=7 Participants	2 day n=5 Participants

PRIMARY outcome

Timeframe: one month after surgery

Population: Primary outcome measure was interval from surgery to discharge. Discharge means that the patient returns back to his home and not to a rehabilitation center.

The primary outcome measure was the interval from surgery to discharge. Discharge means that the patient returns to his home.

Outcome measures

Measure	Control Group n=48 Participants For subjects enrolled in this arm, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group n=46 Participants Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
the Postoperative Length of Stay	18 day Inter-Quartile Range 5.6 • Interval 15.0 to 22.0	14 day Inter-Quartile Range 4.3 • Interval 13.0 to 18.0

SECONDARY outcome

Timeframe: 30 days postoperative

Population: The number of patients with successful implementation of the ONP in the experimental group.

Successful implementation of the ONP was achieved if the patient followed the protocol and did not need PN.

Outcome measures

Measure	Control Group n=46 Participants For subjects enrolled in this arm, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
Successful Implementation Rate of the ONP in the Experimental Group	40 participants	—

SECONDARY outcome

Timeframe: 30 days postoperative

Number of administered PN per group

Outcome measures

Measure	Control Group n=48 Participants For subjects enrolled in this arm, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group n=46 Participants Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
Number of Administered PN	435 number of PN	24 number of PN

SECONDARY outcome

Timeframe: 30 days postoperative

The time to resumption of full diet between the two groups was compared.

Outcome measures

Measure	Control Group n=48 Participants For subjects enrolled in this arm, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group n=46 Participants Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
The Time to Resumption of Full Diet.	8 day Interval 6.0 to 9.0	4 day Interval 3.0 to 5.0

SECONDARY outcome

Timeframe: 30 days postoperative

Number of patients with one or more postoperative complication were compared betweent the two groups.

Outcome measures

Measure	Control Group n=48 Participants For subjects enrolled in this arm, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group n=46 Participants Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
Patients With One or More Postoperative Complication.	37 participants	32 participants

SECONDARY outcome

Timeframe: 30 days postoperative

The number of postoperative complications per patient was compared between the two groups.

Outcome measures

Measure	Control Group n=48 Participants For subjects enrolled in this arm, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group n=46 Participants Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
The Number of Postoperative Complications Per Patient.	1 number of postoperative complications Interval 1.0 to 2.0	1 number of postoperative complications Interval 0.0 to 2.0

SECONDARY outcome

Timeframe: 30 days postoperative

Patients with a catheter related bloodstream infection were compared between the two groups

Outcome measures

Measure	Control Group n=48 Participants For subjects enrolled in this arm, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group n=46 Participants Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
Patients With a Catheter Related Bloodstream Infection	4 participants	0 participants

SECONDARY outcome

Timeframe: 30 days postoperative

The type of postoperative complications (POCs) were compared between the two groups. The type of POCs were classified using the Clavien-Dindo Classification. Herein POCs were classified into 8 categories (1. Infection, 2. Fistula/leak, 3. Bleeding/hematoma, 4. Gastrointestinal, 5. Cardiopulmonary, 6. Neurologic, 7. pain and 8. Other) and stratified by their severity grade (Table 2). Per patient, multiple complications are possible.

Outcome measures

Measure	Control Group n=48 Participants For subjects enrolled in this arm, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group n=46 Participants Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
The Type of Postoperative Complications. 1. Infection	21 number per type of POC	13 number per type of POC
The Type of Postoperative Complications. 2. Fistula or leak	1 number per type of POC	2 number per type of POC
The Type of Postoperative Complications. 3. Bleeding or hematoma	5 number per type of POC	2 number per type of POC
The Type of Postoperative Complications. 4. Gastro-intestinal	13 number per type of POC	16 number per type of POC
The Type of Postoperative Complications. 5. Cardiopulmonary	13 number per type of POC	4 number per type of POC
The Type of Postoperative Complications. 6. Neurologic	0 number per type of POC	5 number per type of POC
The Type of Postoperative Complications. 7. Pain	2 number per type of POC	0 number per type of POC
The Type of Postoperative Complications. 8. Other	15 number per type of POC	11 number per type of POC

SECONDARY outcome

Timeframe: 30 days postoperative

Severity grade of postoperative complications (POCs) was compared between the two groups. The severity grade of POCs were classified using the Clavien-Dindo Classification. Per patient, multiple complications are possible.

Outcome measures

Measure	Control Group n=48 Participants For subjects enrolled in this arm, PN was part of the routine postoperative care pathway. PN was initiated the day postoperatively and was continued until the patients were able to tolerate solid food. PN consisted of Olimel® N7E 1000, 1500 ml or 2000 ml, a parenteral solution with a non-protein energy of 960 kcal/1000ml and containing polyamino-acids (43.75g/1000 ml), glucose (140g/1000ml), lipids (40g/1000ml) and electrolytes. The amount of PN administered depended on non-protein requirement, calculated by 25 kcal/kg ideal body weight ± 10%. Cernevit®, a multivitamin powder for injection, and Addamel®, a trace elements containing concentrate for injection, were added to the PN daily. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician.	Oral Nutrition Protocol (ONP) Group n=46 Participants Subjects enrolled in this arm will undergo the ONP protocol. Oral intake was increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used were Fortimel Juicy®, 200 ml containing 300 kcal (total energy). A detailed description of the content of Fortimel Jucy® is available on www.nutriciamedical.be. Supplementary fluids, up to two liter per day, was given intravenously, if deemed necessary by the treating physician. If the patient was unable to produce stools on the third day post-surgery, neostigmine (Prostigmine® 0.5 mg subcutaneous, maximum four times a day), promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel \[14\], could be administered. Only if oral intake was still insufficient after five days, as defined by the opinion of the treating physician, PN could be initiated in this group.
Severity Grade of Postoperative Complications. Severity Grade 1 Clavien Dindo	15 number of POCs per severity grade	16 number of POCs per severity grade
Severity Grade of Postoperative Complications. Severity Grade 2 Clavin Dindo	35 number of POCs per severity grade	23 number of POCs per severity grade
Severity Grade of Postoperative Complications. Severity Grade 3a Clavien Dindo	16 number of POCs per severity grade	12 number of POCs per severity grade
Severity Grade of Postoperative Complications. Severtity Grade 3b Clavine Dindo	4 number of POCs per severity grade	2 number of POCs per severity grade

Adverse Events

Control Group

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Enhanced Recovery Oral Nutrition Protocol (ERONP) Group

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Control Group n=48 participants at risk Subjects enrolled in this arm will undergo usual medical and pharmaceutical care. In this group, parenteral nutrition (Oliclinomel N7) is part of the routine postoperative care program.	Enhanced Recovery Oral Nutrition Protocol (ERONP) Group n=46 participants at risk Subjects enrolled in this arm will undergo the ERONP protocol. An enhanced oral nutrition protocol (ERONP) with restrictive instructions for parenteral nutrition is implemented. Oral intake is increased progressively with oral fluids and easily digestible food, independent of clinical bowel movements. The oral energy sips used are Fortimel Juicy® (Nutricia) 200 ml containing 300 kcal. This provides supplementary energy and essential nutrients. Supplementary fluid, approximately up to two liter, is given intravenously. If the patient is unable to produce stools on the third day post-surgery, neostigmine (Prostigmin® 0.5 mg subcutaneous, maximum 4 times a day), an acetylcholinesterase inhibitor promoting the movement of intestinal contents by augmenting motor activity of the small and large bowel, can be administered. Only if oral intake is still insufficient after five days, PN (Oliclinomel N7) can be initiated.
Infections and infestations Infection	41.7% 20/48 • Number of events 21 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.	28.3% 13/46 • Number of events 13 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.
General disorders Fistula or leak	2.1% 1/48 • Number of events 1 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.	4.3% 2/46 • Number of events 2 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.
General disorders Bleeding	10.4% 5/48 • Number of events 5 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.	4.3% 2/46 • Number of events 2 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.
Gastrointestinal disorders DGE/Nausea&vomiting	20.8% 10/48 • Number of events 13 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.	32.6% 15/46 • Number of events 16 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.
Cardiac disorders Cardiopulmonary	22.9% 11/48 • Number of events 12 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.	8.7% 4/46 • Number of events 4 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.
Nervous system disorders Neurologic	0.00% 0/48 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.	6.5% 3/46 • Number of events 5 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.
General disorders Pain	4.2% 2/48 • Number of events 2 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.	0.00% 0/46 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.
General disorders Other	27.1% 13/48 • Number of events 15 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.	23.9% 11/46 • Number of events 11 • 30 days Number of patients with one or more postoperative complications (POC), number of POCs per patient and type and severity grade of POCs. The type and severity of POCs were classified using the Clavien-Dindo classification16. POCs were classified into 11 categories and stratified by severity.

Additional Information

Peter Declercq

Pharmacy Department, University Hospitals Leuven & Department of Pharmaceutical and Pharmacological Sciences, KULeuven, Belgium

Phone: 003216342340

Email: peter.declercq@uzleuven.be

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place