Nijenhuis‐Rosien 2019.
| Methods | RCT (parallel) Study design: Quadruple blind Sample size calculation: Yes Diagnosis mycology: Microscopy, culture, and PCR Big toenail specified: Yes Statistical comparisons for outcomes: Yes Duration of follow‐up: 1 year Time points of measurement: At weeks 30 and 52 Location: Innofeet, Zwole, The Netherlands |
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| Participants | Total n: 63 Age: Median (IQR) Laser = 70.5 (60.7, 73.8); Sham = 66.3 (60.9, 71.1) Sex: Laser, 12 women and 20 men; Sham, 9 women and 22 men Inclusion criteria: Type 1 or type 2 diabetes, over 18 years old, clinical suspicion with microbiologic confirmation of onychomycosis, participant is at risk for diabetic foot ulcers defines as Simms score 1, 2 Exclusion criteria: People without the microbiological confirmation of fungal nail infection, Sims classification of 0 or 3, people with an active or history of a diabetic foot ulcer, people who used systemic or topical anti fungal agents during the preceding 3 months, people with ischaemic rest pain, people with ankle brachial index < 0.9, people with a documented toe pressure below 50 mmHg, people receiving dialysis, severe renal insufficiency (eGFR below 30 ml/min), people with an insufficient knowledge of the Dutch language to understand requirements of the study, people with a dark skin colour (Fitspatrick 4 and 5), people who use immunosuppressive medication, people suffering from nail psoriasis, lichen planus, or other abnormalities that could result in clinically abnormal toenails, and a history of epilepsy Disease duration: Unknown Comparable at baseline: Unknown Causative species: T. rubrum most common, in 78% of laser participants and 71% of sham participants. Other dermatophytes and non‐dermatophyte moulds present Number of people lost to follow‐up: None Trial duration: March 2015 ‐ July 2016 |
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| Interventions | Treatment duration: Participants are treated with laser session in weeks 0, 2, 4, and 12 Intervention in study arm 1: Nd:YAG laser pulse therapy (1064 nm), n = 32 Intervention in study arm 2: Sham treatment, n=31 |
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| Outcomes | Complete cure (completely normal nail or, negative mycological results where < 5% target nail affected) at 52 weeks Microbiologic cure at 52 weeks Recurrence (same causative species at baseline and week 52, with negative mycology at week 30) Adverse events: reported |
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| Notes | Not industry funded, foundation grant‐funded. One of the employers of the lead author had a stake in a medical device supply company that includes the device in the current study, but the lead author has no stake in this company. All other authors have no conflicts of interest | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Randomisation was done in blocks (5 blocks of 10 and 1 block of 14) by a third party using sealed, non‐transparent envelopes." Comment: Specific randomisation method that is suitable was specified |
| Allocation concealment (selection bias) | Low risk | Quote: "The investigators, patients, outcome assessors, and statistician were blinded for allocation." Comment: Randomisation was performed by a third party and not study investigators. Allocation concealment was appropriate |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "patients were blinded by inserting a hanging barrier (a plain cloth) between the patients' head and his or her feet. In addition, a blinded laser safety goggle was worn by the subjects. During the procedure, the laser was actually turned on but blasted in a fireproof dish, which was placed next to the foot. The procedural sounds and lights during the laser application and sham procedure were identical." "No participant reported knowing about his or her treatment group." Comment: Blinding was adequate |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: Personnel performing treatment were different from study investigators, outcome assessors, and the statistician. Blinding was adequate |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: Reasons for participants discontinuing the study were provided for each treatment group. The ITT population was clearly specified |
| Selective reporting (reporting bias) | Low risk | Comment: Outcomes reported in published trial protocol are explicit. The same outcomes are specified and reported verbatim in the publication. NCT01996995 |
| Other bias | Low risk | Comment: Not a multiple intervention trial, all outcomes reported for interventions |