Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000840088
Ethics application status
Not yet submitted
Date submitted
4/10/2010
Date registered
6/10/2010
Date last updated
1/05/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Single Patient Multiple Cross-Over Trials To Determine The Efficacy Of Pilocarpine In Relieving Dry Mouth In Patients With Cancer
Scientific title
Single Patient Multiple Cross-Over Trials To Determine The Efficacy Of Pilocarpine In Relieving Dry Mouth In Patients With Cancer
Secondary ID [1] 252814 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dry Mouth In Advanced Cancer Patients 258324 0
Condition category
Condition code
Cancer 258510 258510 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Active pilocarpine 4% (40 mg/ml) drops; Pilcoarpine (po) 2-3 drops 3 times daily (4-6 mg three times daily) with meals in raspberry water delivered as a mouth dropper.

Rasberry water is combined with the active treatment in order to simulate the taste of the placebo, rasberry water. This is to ensure the patient remains blind to the treatment.

The active treatment will be administered in a cycle pair. A cycle pair is a course of treatment over 6 days. For 3 consecutive days, the patient will take the active treatment followed by 3 days on placebo. The duration of the trial will consist of 3 cycle pairs taking place over 18 days. A follow-up on day 19 by the patients physician will then take place.

A washout period will be instigated on the first day of each cycle. On that day, no measurements will be taken.
Intervention code [1] 257338 0
Treatment: Drugs
Comparator / control treatment
Placebo (raspberry water)
Control group
Placebo

Outcomes
Primary outcome [1] 259346 0
Symptomatic improvement measured by mean Numerical rating scores (NRS) for average dry mouth
Timepoint [1] 259346 0
Measured over last 24hours on day 2 and 3 of cycle pair
Secondary outcome [1] 265805 0
A mean xerostomia inventory. The xerosotmia inventory is a self-taken questionnaire to be completed every day by the patient.
Timepoint [1] 265805 0
The mean xerostomia inventory will be measured daily while patient is taking treamtent. Therefore, the measurement will take place over 18 days.
Secondary outcome [2] 265806 0
Oral health related quality of life. The oral health related quality of life is a self taken questionnaire.
Timepoint [2] 265806 0
The oral health related quality of life questionnaire will be taken at the end of each treatment period. Therefore, the questionnaire will be taken every 3 days over an 18 day period.
Secondary outcome [3] 265807 0
Adverse events are measured daily on the self taken questionnaires (stated above) and also by phone calls every 3 days by a research nurse.
Timepoint [3] 265807 0
Measured daily by questionnaires. Measured every 3 days by phone call conversations with research nurse.
Secondary outcome [4] 265808 0
Dysphagia
Timepoint [4] 265808 0
Measured daily using numerical rating score until end of trial (over 18 day period)
Secondary outcome [5] 265809 0
Dysgeusia
Timepoint [5] 265809 0
Measured daily using numerical rating score until end of trial (over 18 day period)
Secondary outcome [6] 265810 0
Global impression of change is a self taken questionnaire.
Timepoint [6] 265810 0
Measured at the end of every 3 day cycle over the duration of the trial (18 days)

Eligibility
Key inclusion criteria
1. Patients aged >=18 years with advanced malignant disease;
2. a clinical diagnosis of chronic dry mouth that has been present for at least 2 weeks with no likelihood of resolution during the trial period
3. a numerical rating scale (NRS) score of >=3 on a 10-point xerostomia scale;
4. liver function (Asparate Transaminase (AST), Alanine Transaminase (ALT)) =< 1.5x upper limit of normal, and total bilirubin within normal range within the week prior to trial registration;
5. no known allergy or sensitivity to pilocarpine;
6. ability to give fully informed written consent and complete all trial requirements.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. no plan to change any medication with the potential to cause dry mouth within the trial period. Patients already on pilocarpine are eligible but must stop these drugs 1 week before trial commencement.
2. no intervention e.g. radiotherapy, chemotherapy, surgery that might alter dry mouth symptoms during the 2 weeks prior to the study period or plans to undergo such therapy during the study period
3. ocular problems contraindicating the use of parasympathetic agents (eg irido-cyclitis, increased intra-ocular pressure);
4. other comorbidity where there is a risk of worsening co-existing medical problems during the trial period and/or active treatment is contemplated eg severe or uncontrolled asthma or pulmonary disease, uncontrolled hypo-or hypertension, hyperthyroidism, uncontrolled seizures or cardiac arrythmias, (especially bradycardias) and Parkinson's disease;
5. a poor understanding of written or spoken English that would preclude completion of all trial requirements
6. an active oral infection i.e. candidiasis, herpetic infections, mucositis, mouth ulcers

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)
Potentially eligible patients (NRS >=3/10) or clinical diagnosis of dry mouth will be identified and screened by research personnel. Those interested in participating in the study will undergo a formal interview in which the purpose and requirements of the trial are fully explained. Fully informed patients will be asked to sign a written consent. Eligibility can then be confirmed and baseline investigations undertaken. Alternate management strategies are discussed with patients who are ineligible to join the study. The pilocarpine/placebo prescription will be written and sent to the hospital pharmacy. The hospital pharmacy will release drug and placebo bottles to the patient according to the randomisation schedule. Participants will be given 6 bottles of liquid medication, numbered 1-6, 3 of which will contain placebo and 3 of which will contain active drug. They will be given daily diaries and written instructions on how to take the medication and from which bottle every day. Participants will be contacted every 3 days, (or daily if there are any concerns) to ensure diary completion and to assess any adverse events. In-patients will be visited daily, preferably at the same time each day. Any adverse event will trigger a formal patient review.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The subjects medication will be randomised based on a randomly generated computer sequence produced by the pharmacy
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
In a Single Patient trial, the patient typically undergoes 3 pairs of treatment periods. As Pilocarpine has a short half life (0.76 hours (5 mg tabs), or 1.35 hours (10 mg tabs) (21), the clinical effect is rapidly evident. Therefore, an appropriate duration of each “treatment” period is 3 days (thus each treatment pair is 6 days), making a total of 18 days for patients who complete the full trial. Patients who fail to complete the full trial will contribute completed cycles to the final analysis. In order to account for medication or placebo “wash out”, no measure of efficacy is taken on the first day of each 3-day period. The order of drugs in each cycle will be determined by random allocation, blinded to both clinician and patient. Patients complete a daily diary recording symptom scores using validated measures for dry mouth and related symptoms, the presence of any side effects, which treatment they prefer, and their estimate of which drug they believe they are taking at the time. At the end of the trial, the order of medications within each of the three cycles is unmasked, and compared with the patient’s observations. Repeated results in the same direction favouring the treatment can be reported in terms of a probability that the result is true. The clinical importance of the result is described by comparing the result to a predetermined clinically important change.

To produce a population estimate of a treatment effect, the results of all succeeding patient cycles are added to the cycles of all preceding patients. An effect size can be calculated between the active medication and placebo cycles, thus providing a population measure of the treatment effect.
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
70
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD

Funding & Sponsors
Funding source category [1] 257793 0
Charities/Societies/Foundations
Name [1] 257793 0
Cancer Council Queensland
Country [1] 257793 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
School of Medicine
Ipsiwich Clinical School
Builidng 11, Level 4
11 Salisbury Road
Ipswich, QLD, 4305
Country
Australia
Secondary sponsor category [1] 256996 0
Charities/Societies/Foundations
Name [1] 256996 0
Cancer Council Queensland
Address [1] 256996 0
553 Gregory Terrace
Fortitude Valley QLD 4006
Country [1] 256996 0
Australia
Other collaborator category [1] 251541 0
Individual
Name [1] 251541 0
Professor Janet Hardy
Address [1] 251541 0
Raymond Terrace,
South Brisbane Qld 4101
Country [1] 251541 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 259818 0
Mater Human Research Ethics Committee
Ethics committee address [1] 259818 0
Ethics committee country [1] 259818 0
Australia
Date submitted for ethics approval [1] 259818 0
14/09/2010
Approval date [1] 259818 0
Ethics approval number [1] 259818 0

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

Contacts
Principal investigator
Name 31732 0
Address 31732 0
Country 31732 0
Phone 31732 0
Fax 31732 0
Email 31732 0
Contact person for public queries
Name 14979 0
Professor Geoffrey Mitchell
Address 14979 0
Ipswich Clinical School
Unversity of Queensland
Buliding 11, Level 4, Room 406
11 Salisbury Road
Ipswich, QLD, 4305
Country 14979 0
Australia
Phone 14979 0
+61 0412 775 117
Fax 14979 0
Email 14979 0
[email protected]
Contact person for scientific queries
Name 5907 0
Professor Geoffrey Mitchell
Address 5907 0
Ipswich Clinical School
Unversity of Queensland
Buliding 11, Level 4, Room 406
11 Salisbury Road
Ipswich, QLD, 4305
Country 5907 0
Australia
Phone 5907 0
+61 0412 775 117
Fax 5907 0
Email 5907 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

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