| Methods |
Randomised controlled trial, single blinded parallel group trial. Primary endpoint of the study was at 15 weeks. Follow‐up at 7, 15 and 27 weeks. |
| Participants |
26 participants, 18 years or older, ankle osteoarthritis based on a recent X‐ray, showing grade II ankle OA (van Dijk score), At baseline patients had to score an AOFAS pain score between 20 and 40; 7 patients in 1 ml group (mean age 31 (range 26 to 84), 4 male, 3 female), 7 in 2 ml group (mean age 47 (range 33 to 63), 3 male, 4 female), 6 in 3 ml group (mean age 51 (range 39 to 71), 5 male, 1 female), 6 in 3 x 1 ml group (mean age 40 (range 21 to 63), 6 female). |
| Interventions |
Four different dosages of hyaluronic acid were randomly allocated from the storage at the outpatient clinic and injected in the ankle joint, i.e. 1, 2, 3 ml and 3 weekly injections of 1 ml. The injection was placed in the anteromedial portal of the ankle joint. |
| Outcomes |
Pain during walking activities (measured with a 100 mm visual analogue scale), Pain at night and during the day while at rest (VAS), General pain (4‐points scale), the amount of rescue medication, safety (reports of adverse events (AEs) |
| Notes |
The study was sponsored by ZImmer, hyaluronic acid was supplied without costs. Zimmer had no involvement in developing the protocol or the manuscript, they only supplied the hyaluronic acid. Data is owned by the authors. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Shuffling envelopes. |
| Allocation concealment (selection bias) |
Low risk |
Opaque sealed envelopes. |
| Blinding of participants and personnel (performance bias)
All outcomes |
High risk |
participants were not blinded, they were randomly allocated to one of the different dosage groups, no comparison to placebo was performed. Outcome might be affected by the expectation to do better with 3 weekly injections than a single injection. |
| Blinding of outcome assessment (detection bias)
All outcomes |
High risk |
Observer was not aware of dose. The participants' reported outcomes might be affected by the fact that people might think they do better from a higher dose of hyaluronic acid. |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
There was a high dropout of participants, however an intention‐to‐treat analysis was undertaken. 9 out of 26 dropouts (35%). |
| Selective reporting (reporting bias) |
Low risk |
Primary and secondary outcomes have been reported in the prespecified way |
| Other bias |
Unclear risk |
The group that received the 2 ml injections performed unexplainably badly. There is insufficient information to permit judgement of low risk or high risk of bias. |
