Severe sialorrhoea (drooling) in children and young people with chronic neurological disorders: oral glycopyrronium bromide

  • Evidence summary
  • ES5
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Evidence tables

Table 4 Mier et al. (2000)

Study reference

Mier RJ, Bachrach SJ, Lakin RC et al. (2000) Treatment of sialorrhea with glycopyrrolate: a double-blind, dose-ranging study. Archives of Pediatrics and Adolescent Medicine 154: 1214–8

Unique identifier

Not known

Study type

RCT

Aim of the study

To evaluate the efficacy and safety of glycopyrronium bromide in the treatment of children with developmental disabilities with sialorrhoea

Study dates

Not stated in the published study. The EPAR reports that the study was conducted from 1998 to 1999

Setting

US (2 centres)

Number of participants

n=39 randomised (27 included in efficacy analysis)

Population

Children and young people aged 4 years and older (mean age 10 years 9 months) with neurodevelopmental conditions and severe sialorrhoeaa

Inclusion criteria

Children aged 4 years and older, with neurodevelopmental conditions and severe sialorrhoea

Exclusion criteria

Not reported

Intervention(s)

2 dosing regimens of glycopyrronium bromide capsulesb, based on the weight of the child:

  • <30 kg: 0.6 mg three times daily, increased weekly by 0.6 mg up to 2.4 mg at week 4

  • >30 kg: 1.2 mg three times daily, increased weekly by 0.6 mg to 3.0 mg at week 4

The maximum tolerated doses were then continued for a further 4 weeks. Doses were increased according to this schedule unless adverse effects occurred or desired 'dryness' (defined by the parent or carer) occurredc,d

Comparator(s)

Placebob

Length of follow-up

8 week treatment phase.

A cross-over design was used: the initial 8 week treatment phase was followed by a 1 week washout period, a 1 week observation period and then 8 weeks of the alternative intervention

Outcomes

Primary outcomee,f:

  • Change in mean mTDS score from baseline to mean maximum (best) score, over 8 weeks

Secondary outcomese:

  • Mean mTDS score after 4 weeks at highest dose by dose level

  • Proportion of patients with ≥4-point improvement in mean mTDS score by dose level

  • Parent or carer assessment of drooling odour

  • Parent or carer assessment of dryness of clothing

Safety outcomes:

  • Any adverse events

  • Adverse events requiring treatment withdrawal

Source of funding

Not reported

Overall risk of bias/quality assessment – CASP RCT checklist

Did the trial address a clearly focused issue?

Yes

Was the assignment of patients to treatments randomised?

Unclearg

Were patients, health workers and study personnel blinded?

Yesh

Were the groups similar at the start of the trial?

Uncleari

Aside from the experimental intervention, were the groups treated equally?

Yes

Were all of the patients who entered the trial properly accounted for at its conclusion?

Yes

How large was the treatment effect?

See table 6

How precise was the estimate of the treatment effect?

See table 6

Can the results be applied in your context? (or to the local population)

Yesj

Were all clinically important outcomes considered?

Yes

Are the benefits worth the harms and costs?

See key points

Study limitations

  • Short‑term study (8 weeks)

  • Only participants who completed the study were included in the analysis. A high proportion of the participants did not complete the study (12/39, 31%)

  • The study did not include an active comparator

  • The study did not report on randomisation and blinding methods

  • It is unclear whether allocation was concealed

Comments

a 34/39 participants had cerebral palsy and 2/39 had tracheostomies (1 of whom dropped out of the study because of excessively thick secretions). 5/39 participants had previously received treatment for sialorrhoea, 3 of whom had taken glycopyrronium bromide and had stopped treatment because of adverse effects.

b Capsules were specially compounded from oral glycopyrronium bromide. Placebo capsules were compounded using identical gelatin capsules.

c The mean highest dose of glycopyrronium bromide for children who completed the study was 2.49 mg (range 1.2–3.0 mg) per dose.

d 4 participants were given these doses twice rather than three times a day, at the parent's request.

e The authors do not specify which outcomes are primary and which are secondary, although mean change in mTDS is reported first in the paper.

f Drooling was assessed weekly in the afternoon (2 hours after a dose) by parents or carers using mTDS.

g Randomisation method and allocation concealment not described.

h Although the study stated that it was double-blind, it was not clear if both investigators and clinicians providing care were blinded.

i Baseline characteristics not reported.

j The study population that completed the trial is not described in detail, and no account is given for the subjects who dropped out.

Abbreviations: EPAR, European Public Assessment Report; mTDS, Modified Teacher's Drooling Scale; RCT, randomised controlled trial.

Table 5 Zeller et al. 2012a

Study reference

Zeller RS, Lee HM, Cavanaugh PF et al. (2012a) Randomized phase III evaluation of the efficacy and safety of a novel glycopyrrolate oral solution for the management of chronic severe drooling in children with cerebral palsy or other neurologic conditions. Therapeutics and Clinical Risk Management 8: 15–23

Unique identifier

NCT00425087

Study type

RCT

Aim of the study

To assess the efficacy and safety of glycopyrronium bromide oral solution in managing problem drooling associated with cerebral palsy and other neurologic conditions in children

Study dates

November 2002 to Apr