Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12614000180617
Ethics application status
Approved
Date submitted
11/02/2014
Date registered
17/02/2014
Date last updated
8/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Compare Loperimide to Placebo for the Prevention of Excess Fluid Losses From the Stoma in Patients with New Loop Ileostomy.
Scientific title
A Double-blind Randomised, Placebo-controlled Trial to Assess the Efficacy of Loperamide versus Placebo as Post-operative Prevention of High Output Ileostomy Losses in Patients with New Loop Ileostomy.
Secondary ID [1] 282764 0
Nil
Universal Trial Number (UTN)
Trial acronym
ALPHI Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
High output ileostomy 289510 0
Dehydration 291129 0
Acute kidney failure 291130 0
Condition category
Condition code
Oral and Gastrointestinal 289837 289837 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Surgery 291507 291507 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Loperamide 4mg three times per day orally for 3 months commencing on day of first passage of flatus post-operatively. Patients will weigh themselves at home daily and keep a diary of stoma output. Empty drug packs will be returned to pharmacy for drug accountability.
Intervention code [1] 287434 0
Treatment: Drugs
Intervention code [2] 288791 0
Prevention
Comparator / control treatment
Placebo administered three times per day orally for 3 months commencing on day of first passage of flatus post-operatively. Patients will weigh themselves at home daily and keep a diary of stoma output. Empty drug packs will be returned to pharmacy for drug accountability.
Control group
Placebo

Outcomes
Primary outcome [1] 289903 0
Incidence of high output ileostomy
Timepoint [1] 289903 0
Whenever the output is greater than 1000mls measured daily for 3 months.
Secondary outcome [1] 303518 0
Serum creatinine above 110 umol/L
Timepoint [1] 303518 0
Monthly for 3 months
Secondary outcome [2] 303519 0
Estimated glomerular filtration rate of less than
60 ml/min/1.73m2
Timepoint [2] 303519 0
Monthly for 3 months
Secondary outcome [3] 303520 0
Participant readmission rate
Timepoint [3] 303520 0
At any time in the 3 months.
Secondary outcome [4] 303521 0
Total hospital length of stay
Timepoint [4] 303521 0
3 months
Secondary outcome [5] 303522 0
Stoma output more than 2 litres per day.
Timepoint [5] 303522 0
Daily for 3 months.
Secondary outcome [6] 303523 0
Serum sodium below 130 mmol/L or above 145mmol/L
Timepoint [6] 303523 0
Monthly for 3 months
Secondary outcome [7] 303524 0
Mean weight loss after hospital discharge
Timepoint [7] 303524 0
3 months.
Secondary outcome [8] 303525 0
Weight loss in excess of 10% after discharge
Timepoint [8] 303525 0
Measured twice weekly for 3 months.
Secondary outcome [9] 303526 0
Surgical complications, according to the validated Clavien Dindo surgical complication score
Timepoint [9] 303526 0
28 days post-operatively from ileostomy formation.

Eligibility
Key inclusion criteria
-Written informed consent
-All adult (>18 years) patients undergoing elective or semi-urgent booked operations involving a loop ileostomy at the participating hospitals.
-Must have passed flatus post-operatively, tolerating diet and no signs and symptoms of ileus.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Refuse or are unable to give written informed consent to participate in the study, or
-Have a known allergy or adverse drug reaction to loperamide
-Pregnant or lactating females
-Have a eGFR less than 60ml/min/1.73m3 pre-operatively

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)
Written informed consent will be provided pre-operatively. Randomisation will occur on the day of first passage of flatus.
Randomisation will be performed by a research nurse, via a centralised web-based randomisation program which will allocate a treatment pack number. The allocated pack number will be dispensed to the patient whilst in hospital by the hospital pharmacy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be computer generated with randomisation to control and intervention in a 1:1 ratio.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on an audit of local data, 60% of patients with a new ileosotomy have an output of greater than 1000 ml/day on discharge from hospital.

In order to detect a clinically relevant difference in the proportion of high output (>1000 ml) of 30%, a study size of 78 (39 in each arm) is needed to detect such a difference with adequate level of significance (alpha 0.05, beta 0.8). Taking into consideration any subject dropouts or withdrawals we calculate we will need a target accrual of 86 patients.
Statistical analysis on the all data will consist of Chi Square and Fishers exact tests to compare categorical data. Continuous data conforming to a normal distribution will be compared using Student's t test.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
31/08/2014
Actual
28/08/2014
Date of last participant enrolment
Anticipated
7/08/2017
Actual
12/07/2016
Date of last data collection
Anticipated
Actual
5/12/2016
Sample size
Target
86
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 1185 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [2] 1186 0
Newcastle Private Hospital - New Lambton Heights
Recruitment postcode(s) [1] 7051 0
2305 - New Lambton Heights

Funding & Sponsors
Funding source category [1] 287536 0
Hospital
Name [1] 287536 0
John Hunter Hospital
Country [1] 287536 0
Australia
Primary sponsor type
Hospital
Name
Hunter New England Local Health District
Address
Lookout Road
New Lambton Heights NSW 2305
Country
Australia
Secondary sponsor category [1] 286288 0
None
Name [1] 286288 0
Address [1] 286288 0
Country [1] 286288 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289514 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 289514 0
Locked Bag 1
New Lambton NSW 2305
Ethics committee country [1] 289514 0
Australia
Date submitted for ethics approval [1] 289514 0
31/05/2013
Approval date [1] 289514 0
04/07/2013
Ethics approval number [1] 289514 0
13/06/19/3.04

Summary
Brief summary
One of the commonest complications of an ileostomy is the potential loss of a large amount of fluids and salts from the ileostomy, and this is called a high output ileostomy. A high output ileostomy can cause a person to become dehydrated and when the losses are large enough, it can lead to kidney failure, and re-presentation to hospital, with admission to hospital with long hospital stay
The purpose of this study is to see if large ileostomy output can be prevented from occurring, rather than waiting for it to happen and then treating it.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 122 122 0 0
/AnzctrAttachments/364522-HREC approval.pdf

Contacts
Principal investigator
Name 41146 0
Dr Stephen Smith
Address 41146 0
Division of Surgery
John Hunter Hospital
Locked Bag 1
Hunter Region Mail Centre NSW 2310
Country 41146 0
Australia
Phone 41146 0
+61 2 49855153
Fax 41146 0
Email 41146 0
[email protected]
Contact person for public queries
Name 41147 0
Ms Rosemary Carroll
Address 41147 0
Division of Surgery
John Hunter Hospital
Locked Bag 1
Hunter Region Mail Centre NSW 2310
Country 41147 0
Australia
Phone 41147 0
+61 2 49855153
Fax 41147 0
Email 41147 0
[email protected]
Contact person for scientific queries
Name 41148 0
Dr Stephen Smith
Address 41148 0
Division of Surgery
John Hunter Hospital
Locked Bag 1
Hunter Region Mail Centre NSW 2310
Country 41148 0
Australia
Phone 41148 0
+61 2 49855153
Fax 41148 0
Email 41148 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.