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Trial registered on ANZCTR


Registration number
ACTRN12618001261202
Ethics application status
Approved
Date submitted
24/07/2018
Date registered
26/07/2018
Date last updated
17/07/2019
Date data sharing statement initially provided
17/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
STIMUlant and osmotic LAXatives in Postoperative Ileus
Scientific title
STIMULAX Study: Open-label randomized controlled trial of a combination of simple STIMUlant and osmotic LAXatives to reduce the duration of postoperative ileus (POI) in patients undergoing colorectal surgery.
Secondary ID [1] 295629 0
Nil known
Universal Trial Number (UTN)
Trial acronym
STIMULAX Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postoperative Ileus 308959 0
Postoperative Complications 308960 0
Colorectal Surgery 308961 0
Condition category
Condition code
Surgery 307858 307858 0 0
Other surgery
Oral and Gastrointestinal 307859 307859 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients in the Intervention group will receive all the medications listed below unless specified otherwise -
• Oral Coloxyl with Senna (1 tablet twice a day - Dioctyl sodium sulfosuccinate (docusate sodium) 50 mg, total sennosides (calculated as sennoside B) 8 mg.) starting the afternoon of surgery (stimulant laxative).
• Oral Movicol (1 sachet = 13.7g, twice a day, powder dissolved in water) starting the afternoon of surgery (osmotic laxative).
• Sodium Phosphate Enema (one enema once a day - each 118ml delivered dose contains sodium phosphate monobasic 19 g/118 mL, sodium phosphate dibasic 7 g/118 mL) from day 1 after surgery, unless left sided anastomosis is performed (osmotic laxative).

Adherence to the intervention would be monitored by routine checking of medication administration charts

Study medications will continue for 10 days postoperatively or until the patient has achieved the study's primary outcome.
Intervention code [1] 301943 0
Prevention
Intervention code [2] 301953 0
Treatment: Drugs
Comparator / control treatment
The Control group will receive standard of care treatment as per our current Enhanced Recovery After Surgery (ERAS) protocol (which as per published guidelines does NOT currently include post-operative laxatives or stimulants).
Control group
Active

Outcomes
Primary outcome [1] 306846 0
Time until the return of gastrointestinal function (GI2) - this is a composite outcome measured by the interval from surgery (in days) until the first passage of stool AND time to tolerance of a solid diet intake for 24hrs. Patients will be reviewed twice per day and assessed by binary (yes/no) questioning of the participant.
Timepoint [1] 306846 0
Patients will be reviewed twice per day from the date of surgery until discharge from hospital (in days)
Secondary outcome [1] 349916 0
Time to first passage of stool (in days) - assessed by binary (yes/no) questioning of the participant.
Timepoint [1] 349916 0
From the date of surgery until discharge from hospital (in days)
Secondary outcome [2] 349917 0
Time to tolerance of solid diet (in days) - assessed by binary (yes/no) questioning of the participant.
Timepoint [2] 349917 0
From the date of surgery until discharge from hospital (in days)
Secondary outcome [3] 349918 0
Time to first passage of flatus (in days) - assessed by binary (yes/no) questioning of the participant.
Timepoint [3] 349918 0
From the date of surgery until discharge from hospital (in days)
Secondary outcome [4] 349919 0
The incidence of Prolonged post-operative Ileus (PPOI) as defined below.

“Prolonged post-operative Ileus (PPOI)” - defined if two or more of the following five criteria are met on or after day 4 postoperatively without prior resolution of “postoperative ileus” (as described above) :
a) Nausea or vomiting
b) Inability to tolerate an oral diet over last 24 h
c) An absence of flatus over last 24 h
d) Abdominal distension
a-d - assessed by binary (yes/no) questioning of the participant.
e) Radiologic confirmation - assessed by checking whether any radiological images were done for the participant
Timepoint [4] 349919 0
From the date of surgery until discharge from hospital (in days)
Secondary outcome [5] 349920 0
Incidence of nasogastric tube re-insertion post-operatively - assessed by direct observation by study personnel and routine checking of inpatient progress notes
Timepoint [5] 349920 0
From the date of surgery until discharge from hospital (in days)
Secondary outcome [6] 349921 0
Length of hospital stay (in days) - assessed by noting it down on study-specific questionnaire and data-linkage to medical records
Timepoint [6] 349921 0
From the date of surgery until discharge from hospital (in days)
Secondary outcome [7] 349922 0
Patient-reported outcome (via Surgical Recovery Score)
Timepoint [7] 349922 0
From the date of surgery until discharge from hospital (in days)
Secondary outcome [8] 349923 0
Time to Readiness for Discharge (in days) as defined by -
I. Passage of flatus or bowel motion, tolerance of oral diet and absence of nausea and vomiting.
II. Mobilisation back to baseline function.
III. Analgesia requirement managed with oral tablets only.
IV. Willingness to be discharged home.

All criteria assessed by binary (yes/no) questioning of the participants
Timepoint [8] 349923 0
From the date of surgery until Time to Readiness for Discharge (in days)
Secondary outcome [9] 349924 0
30-day post-operative complication rate (Clavien-Dindo graded) and reported adverse events. For example - Surgical Site Infection, Pneumonia, Anastomotic leak etc.
Timepoint [9] 349924 0
From the date of surgery until 30 days postoperatively (in days)
Secondary outcome [10] 349925 0
Direct hospital costs - assessed by data-linkage to patient costing database.
Timepoint [10] 349925 0
From the date of surgery until discharge from hospital (in days)
Secondary outcome [11] 349926 0
Incidence of vomiting through reviewing patients in ward rounds, medical progress and nursing notes, self - reported by patients
Timepoint [11] 349926 0
From the date of surgery until discharge from hospital (in days)
Secondary outcome [12] 349927 0
Post-operative analgesics used through medications charts
Timepoint [12] 349927 0
From the date of surgery until discharge from hospital (in days)

Eligibility
Key inclusion criteria
- Adult patients (aged 18 or older) from Central Adelaide Local Health Network catchment area

- Undergoing elective colorectal surgery (including large bowel resections for any indication or undergoing reversal of Hartmann's / loop-ileostomy closure or formation of stoma)

- Able to give informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Under 18 years of age.
• Pregnant and lactating females.
• Allergy to Coloxyl with Senna, Movicol, Sodium Phosphate (Fleet) Enema
• Hyperphosphatemia (> 1.5 mmol/l)
• ASA >=4 due to the higher likelihood or morbidity and mortality, which may confound resulting data.
• Active inflammatory bowel disease
• Colonic Motility disorders (Congenital megacolon, imperforate anus)
• Moderate-Severe Congestive heart failure
• Patients on calcium channel blockers or diuretics with significant electrolyte abnormalities
• Patients with established Ileus as suggested by needing to place a nasogastric tube for decompression, vomiting and unable to tolerate food
• Intestinal obstruction or perforation
• Patients with abdominal pain of unknown cause
• Moderate to severe renal impairment (eGFR < 45 based on two samples a minimum 90d apart).
GFR will be calculated using the Cockcroft Gault equation for creatinine clearance:
CrCl ml/min = [140-age(years)] x bodyweight (kg) / R x serum creatinine (micromol/L)
R = 0.815 for males, 0.85 for females
• Severe hepatic impairment (Child-Pugh class C )
• Inability to give consent or participate in post-operative assessments due to dementia, cognitive impairment and/or language barrier.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Yes - Central randomization using Rand Corporate Random Number Digit Table with allocation and sequence concealed in sealed envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Central randomization using Rand Corporate Random Number Digit Table with allocation
and sequence concealed in sealed envelopes.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The a priori power calculation was carried out using G*Power 3.1 based on best available published data (ALCCaS Trial) which showed the mean duration of POI (duration prior to first bowel motion) following elective colorectal surgery to be 4.65 days (SD 2.15). It was estimated that if therapeutically active, stimulant and osmotic laxatives may be reasonably expected to reduce the mean duration of POI by one day to 3.65 days. A reduction from 4.65 to 3.65 days would also represent a shift which would be clinically significant in practice.

Using a two-tailed independent-samples t-test for the difference between two unpaired means with an alpha-error of 0.05, beta-error of 0.2, and power of 0.8 it was determined that to detect a 22% difference (which is equivalent to a reduction of a day) in duration of POI between groups with an allocation ratio of 1:1, 64 patients would be required in each arm. It was anticipated some participants may be excluded from analysis after administration of study medication or during the process of the study due to varied reasons and thus a recruitment target of 77 patients in each arm was therefore set.

ANALYSIS AND REPORTING OF RESULTS -
Patient recruitment and flow will be reported and represented in the CONSORT diagram.
Analysis will be carried out using SPSS software (SPSS, Chicago, IL, USA). Results will be presented as Mean +/- Standard Error of Mean. Statistical significance will be accepted at P < 0.05.

The baseline characteristics and the perioperative data of the Control and STIMULAX Group will be compared to identify any significant differences between groups at baseline. The presence of significant differences between Control and STIMULAX Groups in all primary and secondary outcomes will be determined and presented as data tables or figures.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 11498 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 23522 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 300212 0
Hospital
Name [1] 300212 0
The Royal Adelaide Hospital
Address [1] 300212 0
Port Road, Adelaide 5000
South Australia
Country [1] 300212 0
Australia
Primary sponsor type
Hospital
Name
The Royal Adelaide Hospital
Address
Port Road, Adelaide 5000
South Australia
Country
Australia
Secondary sponsor category [1] 299635 0
None
Name [1] 299635 0
Address [1] 299635 0
Country [1] 299635 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301035 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 301035 0
Level 3, Roma Mitchell House
136 North terrace
Adelaide, South Australia, 5000
Ethics committee country [1] 301035 0
Australia
Date submitted for ethics approval [1] 301035 0
17/04/2018
Approval date [1] 301035 0
15/06/2018
Ethics approval number [1] 301035 0
HREC Reference number: HREC/18/CALHN/250; CALHN Reference number: R20180420

Summary
Brief summary
Post-operative ileus (POI) is characterized by impairment of bowel motility and is a common complication after major abdominal surgery in general, and after colorectal surgery in particular. The principal features of POI include nausea and vomiting, inability to tolerate diet, significant abdominal distension and delayed passage of flatus and stool. POI as a complication has the largest overall effect on length of postoperative hospitalization.

The purpose of this open-label randomized controlled trial is to determine the effectiveness of stimulant and osmotic laxatives on reducing the duration of postoperative ileus following bowel resection in an optimized Enhanced Recovery After Surgery (ERAS) setting.

We hypothesize that in an optimized ERAS setting, using a combination of stimulant and osmotic laxatives post-operatively will result in a reduction in the duration of postoperative Ileus.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85658 0
Dr Nagendra Dudi-Venkata
Address 85658 0
Colorectal Surgical Unit, 5E 330 -A, Desk -1, Royal Adelaide Hospital
Port Rd, Adelaide, SA 5000
Country 85658 0
Australia
Phone 85658 0
+61 4 30759215
Fax 85658 0
Email 85658 0
drnags3@gmail.com
Contact person for public queries
Name 85659 0
Dr Nagendra Dudi-Venkata
Address 85659 0
Colorectal Surgical Unit, 5E 330 -A, Desk -1, Royal Adelaide Hospital
Port Rd, Adelaide, SA 5000
Country 85659 0
Australia
Phone 85659 0
+61 4 30759215
Fax 85659 0
Email 85659 0
drnags3@gmail.com
Contact person for scientific queries
Name 85660 0
Dr Nagendra Dudi-Venkata
Address 85660 0
Colorectal Surgical Unit, 5E 330 -A, Desk -1, Royal Adelaide Hospital
Port Rd, Adelaide, SA 5000
Country 85660 0
Australia
Phone 85660 0
+61 4 30759215
Fax 85660 0
Email 85660 0
drnags3@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results