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Trial registered on ANZCTR


Registration number
ACTRN12614000540617
Ethics application status
Approved
Date submitted
8/05/2014
Date registered
21/05/2014
Date last updated
12/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study to explore the safety of pyridostigmine in constipated palliative care patients
Scientific title
A pilot study of to assess the safety of pyridostigmine in palliative care patients already prescribed laxatives receiving medications that deliver an anticholinergic load and proven retention of more than 5 radiopaque markers
Secondary ID [1] 284555 0
Nil known
Universal Trial Number (UTN)
U1111-1156-4936
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Palliative Care 291820 0
Constipation 291819 0
Condition category
Condition code
Oral and Gastrointestinal 292183 292183 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
Oral pyridostigmine 60mg twice daily for seven days.
The medicines for this study will be stored in the pharmacy prior to dispensing.
The used bottles of medication will be collected at the completion of each participant to assess compliance. All unused study medicine will be destroyed on completion of study participation after the number of capsules remaining in the bottle has been counted.
Intervention code [1] 289322 0
Treatment: Drugs
Comparator / control treatment
No treatment.
Participant data from the seven days of taking pyridostigmine will be compared with participant data from the seven days prior to taking pyridostigmine.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292062 0
The primary aim of this study is to examine if it is safe to conduct a phase III study of pyridostigmine with the primary outcome being assessments of the safety of the use of pyridostigmine in palliative care patients.
This will be measured by at least 80% of the subjects to complete seven days of pyridostigmine without significant drug-related Adverse Reactions.
The adverse reactions will be assessed daily using the NCI criteria for specific adverse effects of pyridostigmine including nausea, vomiting, abdominal cramps, diarrhoea, increased bronchial secretions, sweating, bradycardia, hypotension & rash. These are measured on 0-5 scale with a score of 3 or more for any adverse effect meaning that this participant will be withdrawn.
Timepoint [1] 292062 0
After 7 days of receiving pyridostigmine.
Secondary outcome [1] 308156 0
To assess the feasibility of conducting a phase III study by analysing the actual completion rates of those who consent to participate.
Timepoint [1] 308156 0
This data will be collected at study cessation and analysed at the completion of the study.
Secondary outcome [2] 308162 0
To explore the efficacy of pyridostigmine by whether there is an improvement in the person’s self-reported Global impression of change over the first 7 days compared to the second 7 days
Timepoint [2] 308162 0
This will be assessed on day 7 and study cessation (after 7-days of treatment or when the participant ceases taking pyridostigmine) using the Global Impression of Change (GIC) Scale.
Secondary outcome [3] 308161 0
To explore the efficacy of pyridostigmine by comparing if there is a net increase in pain scores as measured by the SAS when the anticholinergic medications people are receiving are as adjuvant agents to improve analgesia.
Timepoint [3] 308161 0
This will be collected in the participant diary using the Symptom Assessment Scale (SAS). This will occur daily from baseline until day 14 or study cessation.
Secondary outcome [4] 308157 0
To assess the feasibility of conducting a phase III study by analysing the acceptability of the study processes.

Acceptability of the study processes will be measured by assessing compliance with the colon transit test; the percentage of completion of the study questionnaires and diary; and compliance with taking pyridostigmine twice daily for seven days.
Timepoint [4] 308157 0
Study cessation.
Secondary outcome [5] 308159 0
To explore the efficacy of pyridostigmine by comparing if there are any changes to baseline laxatives and what rescue laxatives that are consumed before and after the commencement of pyridostigmine.
Timepoint [5] 308159 0
After 7 days of taking pyridostigmine. This data will be collected in the participant diaries and at baseline, day 7 and study cessation (after 7-days of treatment or when the participant ceases taking pyridostigmine).
If the participant ceases taking pyridostigmine prior to the end of the 7 days, the diary will be ceased at the same time.
Secondary outcome [6] 308155 0
To assess the feasibility of conducting a phase III study by analysing the willingness of people to be recruited and clinicians to refer and the reasons for non-recruitment at screening.
Timepoint [6] 308155 0
This data will be collected at screening and analysed at the completion of the study.
Secondary outcome [7] 308158 0
Efficacy of pyridostigmine as assessed by whether or not people achieve a reduction of >11 points from their baseline BFI scores to the BFI scores that they report after 7-days of treatment
Timepoint [7] 308158 0
After 7-days of treatment.
Secondary outcome [8] 308160 0
To explore the efficacy of pyridostigmine by documenting if there is any net difference between people’s reports of pain and abdominal bloating which they perceive to be due to constipation.
Timepoint [8] 308160 0
This will be collected in the participant diary using the symptom section of the daily bowel chart (daily from baseline until day 14 or study cessation).

Eligibility
Key inclusion criteria
Age >18;
English speaking;
Person under the care of a specialist palliative care service receiving medications that are associated with an anti-cholinergic effects based on the Clinician–Rated Anti-cholinergic Drug scale;
Self-assessed as dissatisfied with current experiences of constipation despite receiving laxatives;
A score of more than 30 on the self-reported three-item Bowel Function Index;
An estimated prognosis in the opinion of the treating physician that is sufficient to allow the person to participate in the study;
The person themselves is willing and able to participate;
An intact gastrointestinal system.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous adverse reaction to pyridostigmine;
Past history of bowel obstructions, strictures or history of any diseases affecting bowel transit (e.g. ileus, uncontrolled hypothyroidism, hypercalcaemia), irritable bowel syndrome (IBS), inflammatory bowel disease (ulcerative colitis, Crohn’s disease), history of faecal incontinence or bowel resection);
Diagnosed pelvic disorders that may be a cause of constipation;
Surgery (except for minor procedures) within 60 days of Screening, or planned surgery during study treatment that would influence pain or bowel function or preclude completion of the study;
History of chronic constipation prior to enrolling with palliative care services;
Currently pregnant or planning to become pregnant or breastfeeding;
Faecal impaction (based on a rectal exam);
Prolonged QT syndrome (greater than 0.43sec for males, 0.45 for females)
Medications that are prescribed directly for their anti-cholinergic effects (e.g. Glycopyrrolate for drooling; amitriptyline for loose bowel actions);
Creatinine clearance of < 30 ml/min;
Thrombocytopenia of <50,000 platelets per microlitre precluding rectal interventions
Neutropaenia of <2x109/L
Asthma requiring regular medications;
Ischaemic heart disease or cardiac arrhythmias within the previous 12 months;
Epilepsy requiring medication;
Hyperthyroidism;
Myasthenia gravis treated with pyridostigmine

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
No concealment as this study is an open label pilot study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
No randomisation as this study is an open label pilot study.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/06/2014
Actual
4/07/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 2444 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 4289 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst

Funding & Sponsors
Funding source category [1] 289197 0
Hospital
Name [1] 289197 0
Calvary Mater Newcastle
Country [1] 289197 0
Australia
Primary sponsor type
Hospital
Name
Calvary Mater Newcastle
Address
Edith Street
Waratah
NSW 2298
Country
Australia
Secondary sponsor category [1] 287871 0
Other Collaborative groups
Name [1] 287871 0
Palliative Care Clinical Studies Collaborative (PaCCSC)
Address [1] 287871 0
Flinders University
Department of Palliative and Supportive Services
700 Goodwood Rd
DAW PARK SA 5041
Country [1] 287871 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290972 0
Hunter New England Health HREC
Ethics committee address [1] 290972 0
Ethics committee country [1] 290972 0
Australia
Date submitted for ethics approval [1] 290972 0
31/10/2013
Approval date [1] 290972 0
28/11/2013
Ethics approval number [1] 290972 0
13/11/20/3.02

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48154 0
Prof Katherine Clark
Address 48154 0
Calvary Mater Newcastle
Department of Palliative Care
Edith Street
Waratah
NSW
2298
Country 48154 0
Australia
Phone 48154 0
+61 2 4985 0387
Fax 48154 0
+61 2 4985 0385
Email 48154 0
Katherine.Clark@calvarymater.org.au
Contact person for public queries
Name 48155 0
Naomi Byfieldt
Address 48155 0
Calvary Mater Newcastle
Department of Palliative Care
Edith Street
Waratah
NSW
2298
Country 48155 0
Australia
Phone 48155 0
+61 2 4985 0392
Fax 48155 0
+61 2 4985 0385
Email 48155 0
Naomi.Byfieldt@calvarymater.org.au
Contact person for scientific queries
Name 48156 0
Katherine Clark
Address 48156 0
Calvary Mater Newcastle
Department of Palliative Care
Edith Street
Waratah
NSW
2298
Country 48156 0
Australia
Phone 48156 0
+61 2 4985 0387
Fax 48156 0
+61 2 4985 0385
Email 48156 0
Katherine.Clark@calvarymater.org.au

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
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Documents added automatically
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