Muenzer 2006.
| Methods | Multicentre, multinational, double‐blind, randomised, placebo‐controlled, 53‐week clinical trial. | |
| Participants | Participants between the ages of 5 and 31 years with a diagnosis of MPS II based on both clinical and biochemical criteria were enrolled in the study. Clinical criteria included having any one of the following MPS II‐related abnormalities: hepatosplenomegaly; radiographic evidence of dysostosis multiplex; valvular heart disease; or evidence of obstructive airway disease. The biochemical evidence of MPS II included a documented deficiency in I2S enzyme activity of 10% of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes combined with a normal enzyme activity level of another sulfatase. At baseline all participants were required to reproducibly perform pulmonary function testing and have an abnormal FVC of 80% of predicted. Participants who had a tracheostomy or who had received a bone marrow or cord blood transplant were excluded from the study. | |
| Interventions | Intravenous infusions of idursulfase weekly or EOW at a dose of 0.5 mg/kg, or weekly infusions of placebo. | |
| Outcomes | The primary efficacy endpoint in the trial measured changes from baseline to week 53, combining % predicted FVC as a measure of respiratory function and the 6MWT as a measure of functional capacity.The 6MWT was conducted in accordance with ATS guidelines. The secondary efficacy outcome measurements were: passive JROM; liver and spleen volume by MRI; urinary GAG levels and cardiac LVM by echocardiography. All measurements were made at baseline, weeks 18, 36 and 53. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | We found no information about generation of randomisation sequence. Participants randomised equally to 1 of 3 treatment arms, randomisation was stratified by age and total disease score at baseline data. |
| Allocation concealment (selection bias) | Unclear risk | Not cited. |
| Blinding (performance bias and detection bias) All outcomes | Low risk | All participants received intravenous infusion weekly. Participants randomised to EOW idursulfase dosing received placebo infusion during intervening weeks to maintain blinding. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 94 (97.9%) of 96 participants completed 1 year of treatment. The two participants who did not complete one year of treatment died during the study: 1 participant in the placebo group and 1 participant in the idursulfase weekly group. Neither death was considered by the investigator to be related to the study drug. |
| Selective reporting (reporting bias) | Unclear risk | There are concern about selective reporting, due important clinical outcomes (e.g. LVM index and overnight AHI) were not evaluated. |
| Other bias | Low risk | The study apparently was free of other problems that could put it at a high risk of bias |
6MWT: 6‐minute‐walk‐test AHI: apnoea‐hypopnoea index ATS: American Thoracic Society EOW: every other week FVC: forced vital capacity JROM: joint range of motion I2S: iduronate‐2‐sulfatase LVM: left ventricular mass MRI: magnetic resonance imaging