Wraith 2004.
| Study characteristics | ||
| Methods | Multicentre, multinational, double‐blind, randomised, placebo‐controlled, 26 week clinical study. This was a parallel study with 22 participants in the laronidase group and 23 in the placebo group. | |
| Participants | Patients between the ages of 6 ‐ 43 years with a diagnosis of MPS I based on both clinical and biochemical criteria. Clinical criteria included: patients had to be at least 5 years old, able to perform a reproducible FVC that was less than or equal to 80% predicted, able to stand independently and walk a minimum of 5 metres in 6 minutes. Biochemically they had to have iduronidase activity < 10% of normal as measured in fibroblasts or leukocytes. Patients were excluded based on prior tracheostomy or bone marrow transplantation, pregnancy or lactation, administration of an investigational drug within 30 days before study enrolment, any condition which may affect compliance or known hypersensitivity to laronidase or components of the laronidase or placebo solutions. | |
| Interventions | Intravenous infusions of laronidase 0.58 mg/kg or placebo weekly for 26 weeks. | |
| Outcomes | Primary efficacy outcomes were change from baseline to 26 weeks in terms of FVC and 6MWT. These measures both reflecting endurance capacity. Secondary outcome measures were adverse events, antibody production, improvement in nocturnal hypoventilation and apnoea, quality of life and mortality. | |
| Notes | Data from the extension study are not included in the review. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No information provided about generation of randomisation sequence. Patients randomised equally to 1 of 2 arms. |
| Allocation concealment (selection bias) | Unclear risk | No information provided in the paper. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | All patients completed the study. |
| Selective reporting (reporting bias) | Low risk | No concerns. |
| Other bias | Low risk | No other sources of bias identified. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Patients were blinded. Unclear regarding personnel. |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Not clear if assessors were blinded. |
FVC: forced vital capacity 6MWT: 6‐minute walk test