Povidone-iodine ear wash and oral cotrimoxazole for chronic suppurative otitis media in Australian Aboriginal children: a randomised controlled 2x2 factorial design trial
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Objectives
To compare the effectiveness of povidone-iodine ear wash compared to no ear wash and oral cotrimoxazole compared to placebo given in addition to standard topical antibiotic treatment (ciprofloxacin drops) for chronic suppurative otitis media (CSOM) in Australian Aboriginal children.
Methods
A randomised, parallel, 2 x 2 factorial design, assessor-blinded clinical trial in the remote Northern Territory of Australia. Aboriginal children with confirmed CSOM were eligible to be randomised into four treatment groups, allowing two primary treatment comparisons in a 2-in-1 trial approach. Participants received standard treatment (twice daily cleaning and topical ciprofloxacin drops) plus: i) either 16 weeks of pre-treatment povidone-iodine ear wash or no povidone-iodine ear wash; and ii) either 16 weeks of oral cotrimoxazole or placebo. Central randomisation with allocation concealment and triple-blinding of the oral antibiotic treatment arms was used. The relative risk (RR) and risk difference (RD) were estimated after adjustment for age, community, and the other intervention.
The primary outcome was the proportion of children with any otorrhoea (clinical failure) after 16 weeks of treatment. Secondary outcomes included size of tympanic membrane (TM) perforation and amount of discharge, time to cessation of discharge, proportion of children with respiratory and other pathogens in ear discharge (at baseline and 16 weeks) and hearing levels (at 12 months).
Findings
280 children with CSOM were randomised and 270 had their primary outcome assessed. Clinical failure (presence of any ear discharge) after 16 weeks of treatment was 66/134 (49%) in the povidone-iodine group versus 69/136 (51%) in the no povidone-iodine group (RD= −1% (−12,11), p= 0·93) and 56/134 (42%) in the cotrimoxazole group versus 79/136 (58%) in the placebo group (RD= −16% (−28,-4), p=0·007). The amount of discharge, TM perforation size, the level of hearing impairment, and serious adverse events were not significantly different in both treatment comparisons. Anaerobic growth (24%), Pseudomonas aeruginosa (21%) and Haemophilus influenzae (17%) were the most common pathogens found in the ear discharge before treatment. Fungi or yeast (24%), Staphylococcus aureus (15%), and anaerobic growth (10%) were the common pathogens after 16 weeks of treatment, with no significant differences between groups. At 12 months post-randomisation, 55-60% of children had at least one discharging ear and there was no difference between treatment groups.
Interpretation
Povidone-iodine ear washes did not contribute to better ear outcomes in this study. Cotrimoxazole for 16 weeks resulted in more children with clinical improvement to dry ears. Oral cotrimoxazole may play a role in reducing the burden of CSOM in populations with high rates of persistent disease.
Funding
This study is funded by the National Health and Medical Research Council (NHMRC) grant number: 1060764.
Research in context
Evidence before this study
There are three clinical trials relevant to the chronic suppurative otitis media (CSOM) treatments used in this study, two using povidone-iodine, and one of oral cotrimoxazole. Neither of the povidone-iodine trials showed impact from treatment. The trial of 6-12 weeks oral cotrimoxazole demonstrated benefit (15% increased clinical cure). The beneficial effect was not sustained, and the study was not placebo controlled.
Added value of this study
This placebo-controlled factorial randomised controlled trial tests the efficacy of oral cotrimoxazole and povidone-iodine in a group of high-risk children. It combines clinical, hearing, and microbiological outcomes. We demonstrate the efficacy of oral cotrimoxazole for up to 16 weeks for children with CSOM.
Implications of all the available evidence
The best available evidence supports the use of cotrimoxazole as an adjunct therapy. A course longer than 12 weeks may be required to support clinical cure. The beneficial effect of cotrimoxazole did not persist to the 12 month follow up. The use of topical povidone-iodine as an adjunct therapy for CSOM is not supported.
