Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000705987
Ethics application status
Approved
Date submitted
6/07/2011
Date registered
8/07/2011
Date last updated
8/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Can less be better? Is it possible to improve constipation symptom control in palliative care patients when the underlying causes of bowel dysfunction are objectively assessed?
Scientific title
A multi-site cluster randomised controlled trial comparing the severity of constipation symptoms experienced by palliative care patients receiving usual care compared to those diagnosed and managed according to the underlying pathophysiology.
Secondary ID [1] 262582 0
Nil
Universal Trial Number (UTN)
U1111-1122-6883
Trial acronym
Can Less Be Better Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Constipation 268246 0
Condition category
Condition code
Oral and Gastrointestinal 268378 268378 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
Participants randomised to the intervention arm will undertake the comprehensive assessment at the commencement of the study, allowing allocation to one of three diagnostic sub-categories. These include 1) Slow transit alone; 2) Slow transit and delayed outlet; and 3) Delayed outlet alone. For each category, general and targeted interventions appropriate to the patient population will be trialed. These include general interventions such as hydration, exercise, toileting position and prescribing a toileting routine. Specific interventions for slow transit for example, will include the use of stimulant laxatives and for outlet delay will involve the prescription of a regular suppository.

Participants randomised to the control groups will receive laxatives as recommended in the management of constipation by Australian Therapeutic Guidelines.

The Australian-modified Karnofsky Performance Status (AKPS) will be used to assess eligibility. All patients will undergo the Bowel Symptom Questionnaire (BSQ), Patient Assessment of Constipation Symptoms (PAC-SYM) and the Patient Assessment of Constipation Quality of Life (PAC-QOL) on entry into the study regardless of which group they are allocated to. Family distress questionnaire will also be collected on entry into the study.
Clinical data and diagnostic interventions will also be collected with the investigations including measurement of colon transit times, and assessment of the structures of defecation with balloon expulsion and anal manometry. The investigations will require one week to complete.
For those randomised to the intervention arm, participants will undertake the diagnostic interventions prior to commencing the 14 day study period. Whilst this is underway, participants’ constipation will be managed as per usual care, and they will be asked to complete a 7 day bowel diary.
For those randomised to the usual practice arm, participants will be invited to participate in a sub-study where they undergo the same diagnostic interventions as the intervention group.
All participants will be assessed at day 14 with the PAC-SYM and the PAC-QOL, and family distress questionnaire. Whilst on the study, all people will be asked to fill out a daily diary which includes a bowel chart that records actual bowel movement and type, abdominal pain or bloating, and laxatives used. Finally, the ROME III Questionnaire to allow quantification of the numbers of people who come to palliative care services with a past history of functional constipation, and will allow an assessment as to whether this impacts the severity of symptoms they now experience. People will be stratified according to whether they had a feeling of complete evacuation less or more than 2 days per 7 days. Such stratification will allow a comparison of this with the PAC-SYM and PAC-QOL. The Symptom Assessment Scale (SAS) and any adverse effects will be collected as part of this diary. Participants will also receive a telephone call on day 7 to collect data on diary compliance, side effects and medical care.
Intervention code [1] 266914 0
Treatment: Drugs
Intervention code [2] 266931 0
Treatment: Other
Comparator / control treatment
The control treatment will be laxatives as recommended in the management of constipation by Australian Therapeutic Guidelines.: Palliative Care (2010) as detailed below:

Self-reports of passing soft stool:
docusate+sennoside B 100+16 mg (=2 tablets) orally, once or twice daily.
If second agent needed
bisacodyl 10 mg (=2 tablets) orally, at night, increasing to a maximum of 10 mg twice daily.
+/- bisacodyl 10 mg suppository rectally.

Self-reports of passing hard stool:
docusate+sennoside B 100+16 mg (=2 tablets) orally, once or twice daily
OR
macrogol 3350 1 to 3 sachets in 500 ml of water orally, taken over 2 hours daily.
Control group
Active

Outcomes
Primary outcome [1] 269145 0
To compare whether the constipation severity of participants allocated to a mechanistic approach to the assessment and treatment of constipation within different sub categories have better patient outcomes than people palliated using standard current clinical care using the Patient Assessment of Constipation Symptoms (PAC-SYM).
Timepoint [1] 269145 0
Day 15
Secondary outcome [1] 279024 0
To trial an approach to constipation that enables the underlying problems (slow transit of colonic contents, delayed outlet of colonic contents and their overlap), to be quantified in palliative care patients using well-tolerated and validated diagnostic methods. These are Colon Transit Test, Digital Rectal Examination, Anal Manometry, and Balloon Expulsion Test. For those in the usual practice arm and who agree to participate int he sub-study, the same tests will be performed.
Timepoint [1] 279024 0
Baseline
Secondary outcome [2] 279025 0
To determine the number and type of laxatives used in each arm. This will be collected by a participant diary that is completed daily throughout the study period for both intervention and control arm.
Timepoint [2] 279025 0
Daily throughout the 14 day study period.
Secondary outcome [3] 279026 0
To measure whether changes in quality of life occur both between the study groups and over the time the groups are on the study. A comparison between baseline and exit scores on the PAC-QOL will be made for each participant.
Timepoint [3] 279026 0
Baseline, day 15, follow-up week 2 and 4
Secondary outcome [4] 279027 0
To assess whether there are differences in the frequency with which bowel actions are reported between the two groups. This will be collected by a participant diary that is completed daily throughout the study period.
Timepoint [4] 279027 0
Daily throughout the 14 day study period.
Secondary outcome [5] 279028 0
To assess whether there is a difference between the number of people who achieve a sense of complete evacuation more than two times in each seven days period between the two groups. This will be collected by a participant diary that is completed daily throughout the study period.
Timepoint [5] 279028 0
Daily throughout the 14 day study period.
Secondary outcome [6] 279029 0
To retrospectively consider the management of constipation when usual care is delivered and a person has been allocated to a constipation diagnostic subgroup. Participants in the Intervention Units will complete a 7-day Participant diary whilst undertaking the diagnostic tests. Additionally, participants from the usual practice units, who agree to participate in the sub-study will be allocated to a diagnostic subgroup on completion of the sub-study.
Timepoint [6] 279029 0
Day 15
Secondary outcome [7] 279030 0
To assess whether changes in the SAS scores occur over the time of the study
Timepoint [7] 279030 0
Daily throughout the 14 day study period.
Secondary outcome [8] 279031 0
To assess the relationship between performance status using the AKPS and constipation. The Australian-modified Karnofsky Performance Status (AKPS) will be compared to the Patient Assessment of Constipation Symptoms (PAC-SYM).
Timepoint [8] 279031 0
Baseline, day 7, day 15
Secondary outcome [9] 279032 0
To assess the effect of opioid use on constipation over the 14 day intervention period using a patient diary.
Timepoint [9] 279032 0
Day 15
Secondary outcome [10] 279033 0
To assess the relationship between anti-cholinergic load and constipation. This will be collected by a participant diary that is completed daily throughout the study period. The anticholinerigc load will be calculated based on medications with an anticholinergic load the person is receiving.
Timepoint [10] 279033 0
Baseline and daily diary for 14 days.
Secondary outcome [11] 279034 0
To undertake an economic analysis of the management of constipation in people with a life-limiting illness. The economic analysis will estimate incremental resource use, costs, participant effects and the net clinical benefits of an algorithmic approach versus standard current clinical care in the assessment and treatment of constipation from patient level data collected over 28 days of follow up.
Timepoint [11] 279034 0
Follow-up weeks 2 and 4
Secondary outcome [12] 279035 0
To assess the impact of constipation on family/carer's distress.
Family distress will be assessed using the Caregiver Quality of Life Index - Cancer (CQOLC) which includes questions covering the psychological distress domain whilst also providing a broader measure of carer quality of life.
Timepoint [12] 279035 0
Baseline, day 7, day 15, follow-up weeks 2 and 4

Eligibility
Key inclusion criteria
Life-limiting disease
Aged 18 years or older
Regular use of laxatives
Already receiving one or more laxatives for at least 48 hours, as suggested in the Australian Palliative Care Therapeutic Guidelines
Sufficient proficiency in English to provide consent, complete the study questionnaires and telephone interviews
Willing and able to undertake diagnostic interventions
Able to give fully informed written consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Short-term constipation due to problems such hypercalcaemia or vinca alkylating agents occurring within one month of study
History of bowel obstruction or at high risk of bowel obstruction (peritoneal disease)
History of bowel surgery
Local conditions of the peri-anal area and rectum that would contribute to pain on defecation, require specialist interventions and therefore preclude the necessary investigatons to continue on this study including faecal impaction, anal fissure, haemorrhoids, anal prolapse or rectocele >2cm in size
Thrombocytopenia of <50,000 platelets per microlitre precluding rectal interventions
Allergy to latex
Participants who have participated in a clinical study of a new laxative within one month prior to study entry
Women who are pregnant. Patients at risk of pregnancy must have appropriate and effective contraceptive in place (or appropriate advice from their doctor regarding appropriate birth control)
Any other condition that would interfere with study procedures or assessments in the opinion of the investigators

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All people with a life-limiting illness and a diagnosis of constipation should be referred to the study. The clinician will undertake the initial discussion regarding participation. Obtaining consent for this study will be a process of information exchange between the study staff, the potential participant and any other person the potential participant believes should be included in the discussion. The participant information sheet will be used as a basis for the discussion, which will cover all procedures, benefits, burdens and side effects expected or possible during the study. The participant will be given opportunity (in time and physical capacity) to consider the study and formulate questions. Any questions will be addressed and answered fully.
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The unit of randomisation for this study will be by participant. Individuals will be randomised to either the usual practice arm or the intervention are in a 1:1 ratio. Randomisation tables are developed for each site using random number tables, generated at an independent centre (central registry).
The study nurse will be aware of treatment allocation and will assess participants after 14 days of treatment. The statistician will be blinded to participant’s sub-category and intervention.

Participants at each site will be allocated a series of identifying numbers. A two digit study number, a two digit site number, and a sequential three digit screening number will be allocated on referral to the study. This ID number will be used for all subsequent study documentation for that participant.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The unit of randomisation will be at the participant level.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
6/08/2011
Actual
29/07/2011
Date of last participant enrolment
Anticipated
Actual
1/12/2014
Date of last data collection
Anticipated
Actual
14/04/2015
Sample size
Target
210
Accrual to date
Final
91
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 2494 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 2495 0
Braeside Hospital - Prairiewood
Recruitment hospital [3] 2496 0
Sacred Heart Hospice - Darlinghurst
Recruitment hospital [4] 2497 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [5] 2498 0
Greenwich Hospital - Greenwich
Recruitment hospital [6] 2499 0
Nepean Hospital - Kingswood
Recruitment hospital [7] 2500 0
Westmead Hospital - Westmead
Recruitment hospital [8] 2501 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 4219 0
2310
Recruitment postcode(s) [2] 4220 0
2164
Recruitment postcode(s) [3] 4221 0
2010
Recruitment postcode(s) [4] 4222 0
3002
Recruitment postcode(s) [5] 8142 0
2176 - Prairiewood
Recruitment postcode(s) [6] 8143 0
2298 - Waratah
Recruitment postcode(s) [7] 8144 0
3065 - Fitzroy
Recruitment postcode(s) [8] 8145 0
2065 - Greenwich
Recruitment postcode(s) [9] 8146 0
2747 - Kingswood
Recruitment postcode(s) [10] 8147 0
2145 - Westmead
Recruitment postcode(s) [11] 8148 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 267389 0
Government body
Name [1] 267389 0
Natinal Health and Medical Research Council
Country [1] 267389 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Palliative Care Clinical Studies Collaborative
700 Goodwood Road
Daw Park, SA 5041
Country
Australia
Secondary sponsor category [1] 266449 0
None
Name [1] 266449 0
Address [1] 266449 0
Country [1] 266449 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269362 0
Hunter New England Human Ressearch Ethics Committee
Ethics committee address [1] 269362 0
Locked Bag 7
Hunter regional Mail Centre
Warabrook NSW 2310
Ethics committee country [1] 269362 0
Australia
Date submitted for ethics approval [1] 269362 0
28/02/2011
Approval date [1] 269362 0
24/06/2011
Ethics approval number [1] 269362 0
11/03/16/4.01
Ethics committee name [2] 291060 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [2] 291060 0
St Andrews Place
East Melbourne
Victoria 8006
Ethics committee country [2] 291060 0
Australia
Date submitted for ethics approval [2] 291060 0
Approval date [2] 291060 0
11/01/2012
Ethics approval number [2] 291060 0
HREC/11/PMCC/24

Summary
Brief summary
Constipation is a common, distressing and serious symptom, affecting between 50-90% of people referred to specialist palliative care services, with 40-70% of people failing to achieve adequate symptom control. The number of people failing to achieve satisfactory symptom relief is not acceptable as inadequate symptom relief is responsible for adding to individual and societal burdens. In palliative care, decisions regarding the prescription of laxatives are based predominantly on clinical experience and institutional approaches. Many of these do not consider the pathophysiological basis that underlies the symptom of constipation. This approach is very dissimilar to that adopted by gastroenterologists in the treatment of non-palliative care patients. The most striking difference is the limited information to categorise the palliative population into the groupings that gastroenterologists would routinely use, thereby limiting the ability to tailor interventions to improve symptom control. This study will aim
1). To develop an approach to constipation that enables the underlying problems (slow transit of colonic contents, delayed outlet of colonic contents or an overlap of these problems), to be quantified in palliative care patients using well-tolerated and validated diagnostic methods;
2). To compare whether the constipation severity of those patients randomly allocated to a mechanistic approach to the assessment and treatment of constipation within different sub categories have better patient outcomes than people palliated using standard current clinical care.
Trial website
None
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 32841 0
A/Prof Katherine Clark
Address 32841 0
Calvary Mater Newcastle Locked Bag 7 Hunter regional Mail Centre Warabrook NSW 2310
Country 32841 0
Australia
Phone 32841 0
+61 2 4921 1953
Fax 32841 0
+61 2 4921 1952
Email 32841 0
[email protected]
Contact person for public queries
Name 16088 0
Ms Naomi Byfieldt
Address 16088 0
Calvary Mater Newcastle
Locked Bag 7
Hunter regional Mail Centre
Warabrook NSW 2310
Country 16088 0
Australia
Phone 16088 0
+61 2 4921 1953
Fax 16088 0
+61 2 4921 1952
Email 16088 0
[email protected]
Contact person for scientific queries
Name 7016 0
A/Prof Katherine Clark
Address 7016 0
Calvary Mater Newcastle
Locked Bag 7
Hunter regional Mail Centre
Warabrook NSW 2310
Country 7016 0
Australia
Phone 7016 0
+61 2 4921 1953
Fax 7016 0
+61 2 4921 1952
Email 7016 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
SourceTitleYear of PublicationDOI
EmbaseIdentifying factors that predict worse constipation symptoms in palliative care patients: A secondary analysis.2017https://dx.doi.org/10.1089/jpm.2016.0331
N.B. These documents automatically identified may not have been verified by the study sponsor.