Do pilocarpine drops help dry mouth in palliative care patients: a protocol for an aggregated series of n-of-1 trials

Nikles, Jane; Mitchell, G.; Hardy, Janet; Agar, Meera; Senior, Hugh; Carmont, Sue-Ann; Schluter, Philip J.; Good, Phillip; Vora, Rohan; Currow, David C.

doi:10.1186/1472-684x-12-39

Cited by 11 publications

(19 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…“To describe participants’ overall response, three types of Bayesian results will be presented: (i) the mean of the posterior distribution of the mean difference between placebo and stimulant scores, which gives the best estimate of the overall effect size difference between treatments; (ii) the associated 95% credible region, which give intervals of uncertainty (in this case the 2.5 and 97.5 percentile) of the posterior distributions used in (i); and (iii) the posterior probability of the mean difference that stimulant scores were better than placebo scores, which describes the likelihood that the patients will favour the active treatment in future cycles 34 . A patient will be defined to be a ‘responder’ when these estimated values exceed predefined threshold values 34 .”33…”

Section: Section 3c: Methods—data Collection Management and Analysismentioning

confidence: 99%

See 1 more Smart Citation

SPIRIT extension and elaboration for n-of-1 trials: SPENT 2019 checklist

Porcino¹,

Shamseer

Chan

et al. 2020

BMJ

View full text Add to dashboard Cite

Randomised clinical trials are the preferred method for establishing average intervention effects for groups. Using key methodological elements of these trials, n-of-1 trials provide rigorous evidence of intervention effects for individuals. N-of-1 trials are particularly useful for situations where randomised clinical trials are not always feasible or appropriate, such as for individuals with rare diseases, comorbid conditions, or using concurrent treatments. N-of-1 trials enhance precision when intervention effects are heterogeneous between individuals. Here, we describe an extension to the SPIRIT (standard protocol items: recommendations for interventional trials) guideline, SPENT (SPIRIT extension for n-of-1 trials), to improve the completeness and transparency of n-of-1 trial protocols. SPENT is also aligned with the CONSORT (consolidated standards of reporting trials) extension for n-of-1 trials (CENT). The guideline development group followed the development strategy for reporting guidelines endorsed by the EQUATOR Network. SPENT began with a systematic review for n-of-1 protocol recommendations. After analysis to identify possible SPENT items, a three round Delphi process was implemented, with international participation involving researchers, patient advocates, and other stakeholders. This was followed by in-person meetings and email discussion of the SPENT group to achieve consensus. SPENT has 14 extension items specific to n-of-1 trials, a checklist for n-of-1 trial protocol abstracts, and additional guidance for eight SPIRIT items where trialists could encounter issues specific to n-of-1 trials. This paper describes the rationale and development process, and provides examples and explanations for each SPENT checklist item.

show abstract

Section: Section 3c: Methods—data Collection Management and Analysismentioning

confidence: 99%

“…“For each cycle, data from day 1 will be discarded to allow for a wash-out period, and data from days 2 and 3 will be analysed.”33…”

Section: Section 3c: Methods—data Collection Management and Analysismentioning

confidence: 99%

SPIRIT extension and elaboration for n-of-1 trials: SPENT 2019 checklist

Porcino¹,

Shamseer

Chan

et al. 2020

BMJ

View full text Add to dashboard Cite

show abstract

“…[ 10 ] Similarly, for pilocarpine, the side effect rate is high (usually the result of generalized parasympathomimetic stimulation), and side effects tend to be the main reason for withdrawal. [ 11 12 ] These side effects include sweating, wheezing, abdominal cramps, lacrimation, nausea, vomiting, diarrhea, dizziness, headache, palpitations, asthenia, chills, increased urinary frequency, and rhinitis. These can lead not only to patients’ poor adherence to the pharmacological treatment but also to RAIT.…”

Section: Pharmacological Interventions For Managing Radioactive Iodinmentioning

confidence: 99%

Seeking optimal management for radioactive iodine therapy-induced adverse effects

Charalambous

2017

Asia-Pacific Journal of Oncology Nursing

View full text Add to dashboard Cite

Radioactive iodine therapy (RAIT) is one of the important treatment modalities in the management of differentiated thyroid cancer (DTC). RAIT with iodine-131 has long been used in the management of DTC for the ablation of residual thyroid or treatment of its metastases. Despite being reasonably safe, radioiodine therapy is not always without side effects. Even relatively low administered activities of RAIT used for remnant ablation have been associated with the more clinically significant side effects of sialadenitis, xerostomia, salivary gland pain and swelling, dry eyes, excessive tearing, or alterations in taste in as many as 25% of patients. Given that there is a lack of comprehensive management of these RAIT-induced adverse effects, this paper explores the use of other nonpharmacological measures and their effectiveness as interventions to minimize salivary gland damage.

show abstract

“…A small number of trials have been conducted to investigate the effect of pilocarpine in the alleviation of xerostomia using formulations aimed at mucosal absorption in the mouth rather than systemic absorption from the gastrointestinal tract (GIT). The formulations of pilocarpine were pastilles, lozenges, buccal inserts, mouthwashes and eye drops to be taken by mouth (Bernardi et al, 2002;Gibson et al, 2007;Hamlar et al, 1996;Kim et al, 2014;Nikles, Mitchell et al, 2013;Rupel et al, 2014;Tanigawa et al, 2015;Taweechaisupapong et al, 2006).…”

Section: Research Plan 181 Research Rationalementioning

confidence: 99%

“…Tablets and capsules designed to be swallowed whole were excluded in order to focus on products that could deliver pilocarpine buccally. Pilocarpine has been previously formulated in the form of a buccal insert (Gibson et al, 2007), mouthwashes (Kim et al, 2014;Tanigawa et al, 2015), eye drops administered orally (Nikles et al, 2013), pastilles (Hamlar et al, 1996), lozenges (Taweechaisupapong et al, 2006) and chewing gum (Singh & Singh, 2003). The buccal inserts are not suitable for extemporaneous compounding in community compounding pharmacies.…”

Section: Introductionmentioning

confidence: 99%

Extemporaneously compounded buccal pilocarpine preparations, acceptability and pilot testing for the treatment of xerostomia (dry mouth) in Australia

Estafanos¹

View full text Add to dashboard Cite

Xerostomia, the subjective feeling of dry mouth, is characterised by hypofunctioning salivary glands in which either the quantity or quality of saliva is reduced. It is a common symptom for a variety of diseases such as rheumatic and dysmetabolic diseases, and is the primary symptom associated with Sjögren's syndrome. Xerostomia is also caused by treatments such as radiotherapy to the head and neck region and is a side effect of a range of medications. People with xerostomia usually experience dryness of mouth, lips and throat. They are more susceptible to dental caries, oral mucositis and enhanced tooth decay. They have problems with moistening, chewing and swallowing foods and taste alterations associated with reduction in salivary flow can affect their ability to taste food. These consequences can lead to decreased food consumption, which can cause malnutrition and further suppression of their immune defence mechanisms with increased risk of morbidity and reduced quality of life. Some approaches to managing xerostomia include sipping fluids such as water more frequently to moisten the oral mucosa, chewing sugar free gum to stimulate more saliva secretion, and using saliva replacement gels or drops. However, these strategies often do not provide sufficient relief due to the short-term effect they produce. Thus, a strong rationale exists for the development and evaluation of a medication to help treat dry mouth symptoms. Pilocarpine oral tablets (Salagen) are available in at least 24 countries including the USA, Canada and the UK, and a wide range of countries across Europe, South America and Asia, for the treatment of radiation-induced xerostomia and xerostomia as a result of Sjögren's syndrome. Pilocarpine is a non-selective muscarinic agonist that stimulates the muscarinic cholinergic receptors on the surface of exocrine glands, including salivary glands and sweat glands, resulting in increased salivation and sweating. An oral dose of 5 mg pilocarpine in the form of tablets or capsules to be taken three times daily produces the most effective therapeutic response in terms of subjective relief of dry mouth according to many clinical studies. An oral dosage form of pilocarpine is not commercially available in Australia. Pilocarpine is only commercially available as 1% and 2% eye drops, which are registered on the Australian Register of Therapeutic Goods (ARTG) for the treatment of glaucoma. When these eye drops were given by mouth for the treatment of dry mouth as part of a previous clinical trial, which was done in an inpatient palliative population within a hospital setting, they tasted unpleasant to most of the patients and were not acceptable as a dosage form for dry mouth treatment for that reason. This thesis investigates the potential to use pilocarpine dosage forms that can be compounded in pharmacies for delivering 5 mg

show abstract

Do pilocarpine drops help dry mouth in palliative care patients: a protocol for an aggregated series of n-of-1 trials

Cited by 11 publications

References 28 publications

SPIRIT extension and elaboration for n-of-1 trials: SPENT 2019 checklist

SPIRIT extension and elaboration for n-of-1 trials: SPENT 2019 checklist

Seeking optimal management for radioactive iodine therapy-induced adverse effects

Extemporaneously compounded buccal pilocarpine preparations, acceptability and pilot testing for the treatment of xerostomia (dry mouth) in Australia

Contact Info

Product

Resources

About