A randomised, assessor blind, parallel group comparative efficacy trial of three products for the treatment of head lice in children - melaleuca oil and lavender oil, pyrethrins and piperonyl butoxide, and a "suffocation" product - ClearLice

A randomised, assessor blind, parallel group comparative efficacy trial of three products for the treatment of head lice in children – melaleuca oil and lavender oil, pyrethrins and piperonyl butoxide, and a “suffocation” product

Topic(s) study pertains to

Tea tree oil, Ineffectiveness of OTC treatment

Place of study

BMC Dermatology, Queensland, Australia

Name of Scientist

  • Stephen C Barker
  • Phillip M Altman

Abstract

Background

There are many different types of pediculicides available OTC in Australia. In this study we compare the efficacy and safety of three topical pediculicides: a pediculicide containing melaleuca oil (tea tree oil) and lavender oil (TTO/LO); a head lice “suffocation” product; and a product containing pyrethrins and piperonyl butoxide (P/PB).

Method

This study was a randomised, assessor-blind, comparative, parallel study of 123 subjects with live head lice. The head lice products were applied according to the manufacturer’s instructions (the TTO/LO product and the “suffocation” product were applied three times at weekly intervals according to manufacturers instructions (on Day 0, Day 7 and Day 14) and the P/PB product was applied twice according to manufacturers instructions (on Day 0 and Day 7)). The presence or absence of live lice one day following the last treatment was determined.

Results

The percentage of subjects who were louse-free one day after the last treatment with the product containing tea tree oil and lavender oil (41/42; 97.6%) and the head lice “suffocation” product (40/41, 97.6%) was significantly higher compared to the percentage of subjects who were louse-free one day after the last treatment with the product containing pyrethrins and piperonyl butoxide (10/40, 25.0%; adj. p < 0.0001).

Conclusion

The high efficacy of the TTO/LO product and the head lice “suffocation” product offers an alternative to the pyrethrins-based product.

Trial Registration

The study was entered into the Australian/New Zealand Clinical Trial Registry, ACTRN12610000179033.

Background

The incidence of head louse infestation is high in many countries[123]. This may be explained, in part at least, by the evolution in head lice of lower susceptibility (resistance) to older pediculicides[4]. Two new types of head lice products have found wide acceptance in many countries: essential oil based products and products designed to “suffocate” head lice. It is important to assess and compare the lice kill rates and the safety of these newer products with existing market leading products in well controlled and well designed clinical trials.

One essential oil based product containing 11.0% eucalyptus oil was reported to have an efficacy of 82.5% compared to a kill rate of 36.1% for a product containing pyrethrins and piperonyl butoxide using a study design similar to that employed in this study[5]. In another study a “suffocation” product containing 5% benzyl alcohol was reported to kill all head lice in 92.2% of subjects as measured one day after the second treatment (day 8)[6]. Using the same head lice product containing pyrethrins and piperonyl butoxide, studied by ourselves previously, as a comparator[5], the efficacy and safety of two new head lice products were studied by us: NeutraLice Lotion® (containing melaleuca oil and lavender oil) and NeutraLice Advance® (a “suffocation” product).

Methods

Objectives and Interventions

To compare the efficacy and tolerance of three head lice treatment products when used according to the manufacturers instructions:

  1. 1.

    Product containing melaleuca oil (tea tree oil) 10% w/v and lavender oil 1% w/v (TTO/LO) (NeutraLice Lotion® Key Pharmaceuticals Pty Ltd, Australia) presented as a clear oily solution

  2. 2.

    “suffocation” product containing benzyl alcohol, mineral oil, polysorbate 80, sorbitan monooleate, Carbopol 934, water and triethanolamine (NeutraLice Advance® Key Pharmaceuticals Pty Ltd, Australia) presented as a white opaque lotion

  3. 3.

    Product containing pyrethrins 1.65 mg/g, and piperonyl butoxide 16.5 mg/g (P/PB) (Banlice Mousse® Johnson & Johnson Pacific Pty Ltd, Australia) presented as a pressurised aerosol mousse

Methodology

This was an assessor blind, randomised, parallel group, comparative study. The study population consisted of primary school-aged children (aged 4 yrs to 12 yrs) from three different schools in Queensland and their siblings with live head lice (adults or nymphs) in their hair or on their scalp. If parental written informed consent was provided, the children were screened for the presence of live head lice by visual inspection (see Appendix 1 – Definitions) and by dry-combing (see Appendix 1 – Definitions). Those subjects meeting the entry criteria were randomised and treated with one of the three head lice products. Subjects with a history of allergies, presence of scalp disease and those who were treated with a head lice product in the 4 weeks prior to participation in this trial were excluded.

The TTO/LO and “suffocation” products were applied three times, at weekly intervals, as per the manufacturer’s instructions (on day 0, day 7 and day 14). The P/PB product was applied twice, as per the manufacturer’s instructions (on day 0 and day 7). The louse-combing procedure normally used in combination with these three products was not done so we could compare the efficacy of the components of each product without confounding the efficacy measurements by physically removing head lice by combing (which is a treatment in itself).

The primary outcome measure was the louse free rate (see Appendix 1 – Definitions) assessed one day after the last treatment (at day 15 for TTO/LO and “suffocation” products and at day 8 after application of P/PB product) and was determined by wet-combing (see Appendix 1 – Definitions) for the Intention to Treat population and the Per Protocol population. A secondary outcome measure, louse free rate at day 1, was determined by dry-combing

Ethics

This trial was conducted in compliance with the World Medical Association Declaration of Helsinki, the requirements of the National Statement on Ethical Conduct in Research Involving Humans, ICH E6 Guidance for the Industry; Good Clinical Practice: Consolidated Guidance, the National Privacy Principles and relevant State/Territory laws. The trial activities were approved by the Medical Research Ethics Committee of the University of Queensland, project No. 2003000184 and all parents/guardians provided written informed consent.

Randomisation

Eligible subjects were randomly assigned to receive one of the three head lice treatments by a computer generated code using blocked randomisation (groups of six).

Blinding

This trial was assessor-blind. The person applying the treatment could not avoid being aware of the product being applied as the products are easily identifiable by their physical attributes; however, assessor-blinding was achieved by using different staff for applications on the one hand and assessment and CRF data entry on the other hand, and by physically separating these activities at the investigational site. Subjects were prevented from sighting the products being used. The parents of subjects were also blinded to the treatment applications. Analysts involved in data management were blinded to the identification of each treatment group until the final efficacy analysis for each treatment group was complete.

Treatment of siblings

If an enrolled subject had a primary-school aged sibling (aged 4 years to 12 years), the sibling was also examined for head lice and, if infested with live lice and available for enrolment, this sibling was enrolled into the same treatment arm as the subject. Those siblings not enrolled, because they were unavailable for the trial for any reason or had eggs only, were wet-combed-out at days 0 and 7 for siblings of subjects receiving the P/PB product or wet-combed-out (see Appendix 1 – Definitions) at days 0, 7 and 14 for siblings of subjects receiving TTO/LO and “suffocation” products.

Treatment compliance

The Intent-to-Treat (ITT) population is defined as all subjects receiving at least one treatment application. This was the primary population for determination of safety and efficacy.

Subjects who met all the protocol requirements are termed the per-protocol (PP) population and this was the secondary population for determination of efficacy. Subjects are considered to be per protocol (PP) if they satisfied the requirements listed in Appendix 2:

Dosage and dosage regimen

The doses, method of application and number of weekly treatments were those recommended by the manufacturers. All three products were applied for 10 minutes. After the TTO/LO product was applied the hair was covered by a shower cap made of polyvinyl chloride to retain the volatile components of the formulation. The TTO/LO and “suffocation” products were then washed out with water; the P/PB product was washed out with a standard shampoo. The TTO/LO and “suffocation” products were applied at weekly intervals on days 0, 7 and 14. The P/PB product was applied on days 0 and 7.

Criteria for evaluation of efficacy

The efficacy of each product is defined as the “louse-free rate.” The louse free rate was assessed at day 1 (by dry-combing), and at day 15 (by wet-combing) for those subjects treated with TTO/LO or “suffocation” products OR at day 8 (by wet-combing) for those subjects treated with the P/PB product. In the case of the day 1 examination, dry-combing was used and combing was stopped immediately if live lice were observed. A blinded assessor conducted the hair and scalp examinations.

Often, visual inspection was sufficient to determine if live lice are present especially in cases of severe infestation. In such cases, dry/wet-combing was not necessary to confirm the presence of live lice. However, visual inspection alone was insufficient to declare a subject as “louse-free”.

Criteria for evaluation of safety (tolerance)

Subjects were interviewed on site regarding possible adverse effects during and immediately following the application procedure as well as just before the next scheduled application by site staff. The incidence and severity of adverse events was compared between treatment groups. The ITT population was analysed for safety.

Statistical and data management methods

Determination of sample size and data analysis

Previous efficacy studies involving the P/PB product reported a cure rate of 36.1%[4]. Assuming the efficacy of the TTO/LO and “suffocation” products to be approximately 70% in the ITT population, it was estimated that 40 subjects in each group (assuming clustering, i.e. siblings will receive the same treatment as the first subject enrolled in the family) were required to test the hypothesis of superiority of the TTO/LO and “suffocation” products with a two-sided test using alpha at or less than 0.025 to allow for two pair-wise comparisons with 75% power. For the unadjusted analysis the chi-square test was used. For adjusted analysis the Generalized Estimating Equations methodology was used to fit the logistic regression model to account for the clustering within families.

Results

Efficacy

Subjects were enrolled between April and June 2009. The disposition of subjects is shown in Figure 1. 505 subjects were screened, 132 were enrolled in the study (43 were treated with TTO/LO product, 45 with “suffocation” product and 44 with the P/PB product). Of these 132 subjects (ITT population), 123 subjects were evaluable: 42 TTO/LO subjects; 41 “suffocation” product subjects and 40 P/PB subjects; 9 subjects were not assessed at a final visit. Of the 132 enrolled subjects, 108 were deemed PP; 41 TTO/LO subjects, 37 “suffocation” product subjects and 30 P/PB subjects. Reasons for a subject being deemed not PP were: enrolled sibling not treated with the same product as original subject; use of an alternative head lice treatment during the trial; siblings not available for treatment on same day as original subject; and subjects not available for assessment. There were no subject withdrawals. The day after the last treatment was day 15 for the TTO/LO and “suffocation” products and day 8 for the P/PB product.
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