Cibere J, Kopec JA, Thorne A, et al. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis and Rheumatism 2004;51:738-45.
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/15478160
Full text article: https://onlinelibrary.wiley.com/doi/full/10.1002/art.20697
| Methods | Study design: Randomized double-blind placebo-controlled study with a parallel-design
Number of groups: Two groups |
| Participants | Number of participants: 137 randomized, 134 completed
· Active deprescribing group: 66 randomized, 66 completed · Control group: 71 randomized, 68 completed Age: 65 years (range 43–88 years) Sex: 77 females, 60 males Inclusion criteria: · Osteoarthritis of the knee(s) according to the American College of Rheumatology diagnostic criteria · Kellgren-Lawrence grade 2 on antero-posteriorradiograph of the knee · Current daily use of glucosamine for at least 1 month · At least moderate improvement in knee pain since starting on glucosamine, measured on a 6-point scale of knee pain (worse, unchanged, mildly improved, moderately improved, markedly improved, completely subsided) Exclusion criteria: · Chondroitin sulfate usewithin the previous 2 months · Knee injection with hyaluronate in the previous 6 months or with corticosteroids in the previous 3 months, 3) surgical procedure on either knee in the previous 3 months · Narcotic analgesic use · Uncontrolled medical condition or planned surgery that could interfere with follow-up · Baseline potassium 5.3 mEq/liter or baseline creatinine 120 mmol/liter Concomitant medicines: · As required analgesic medications (e.g. acetaminophen and non-steroidal anti-inflammatory drugs) were allowed and recorded by the patient in a daily diary · Other concomitant treatments were not allowed during the study (including chondroitin sulfate and intraarticular injections with corticosteroids or hyaluronic acid) Country: Canada Setting: Community – four centers in Canada |
| Interventions | Medicine: Glucosamine sulfate formulated as a potassium salt preparation (500-mg tablets)
· Dosage equivalent to glucosamine dose taken before the study with a maximum of 1,500 mg per day · Participants who used a dosage 1,500 mg per day before the study were treated with 1,500 mg per day during the study Withdrawal schedule: Not described Comparator: Placebo compared to continued medicine |
| Outcomes | Disease flare
Function measured using Western Ontario and McMaster Universities Osteoarthritis Index Quality of life measured using EuroQol 5-D utility and visual analog scale |
| Dates | Dates: Not described
Follow-up duration: Six months |
| Funding sources | Mary Pack Research Fund, Vancouver, British Columbia, Canada and by the Doris Alma Mary Anderson Fund for Geriatric Research, London, ON, Canada.
Dr. Cibere’s work supported by a Canadian Institutes of Health Research Clinician Scientist Award and a Michael Smith Foundation for Health Research Postdoctoral Fellowship Award. |
| Notes | Additional information sought, but not received. |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Low risk | “A centralcomputer-generated randomization code was produced by a researcher not affiliated with the study. Block randomization with a randomly variable block size of 2–6 was used.” |
| Allocation concealment (selection bias) | Low risk | “The randomization code was forwarded to the manufacturer of the study medication and was used to label the study medication bottles consecutively from 1 to 160. The randomization codes remained sealed until after the blinded analysis had been carried out. Thus, allocation concealment was maintainedand study investigators and patients were blinded throughout the study. Eligible subjects were assigned the next consecutive study number.” |
| Blinding of participants and personnel (performance bias) | Low risk | “The randomization code was forwarded to the manufacturer of the study medication and was used to label the study medication bottles consecutively from 1 to 160. The randomization codes remained sealed until after the blinded analysis had been carried out. Thus, allocation concealment was maintainedand study investigators and patients were blindedthroughout the study.”
“Glucosamine and placebo tablets were supplied by VitaHealth (Winnepeg, Manitoba, Canada). The active drug consisted of glucosamine sulfate formulated as a potassium salt preparation (500mg tablets). The placebo tablets were indistinguishable from the glucosamine tablets and contained excipients only. Patients were randomized to receive either glucosamine sulfate or placebo.” |
| Blinding of outcome assessment (detection bias) | Low risk | Outcome assessors were firstly the patients themselves (who were blinded), and then a physician global assessment was made – the physicians also being blinded by the separation of randomization and placebo preparation from the rest of the investigators. |
| Incomplete outcome data (attrition bias) | Low risk | An intention-to-treat analysis was used. It was decided a priori that patients who were lost of follow-up would be considered to have an exacerbation for the purpose of the primary analysis. For the survival analysis, patients lost of follow-up were right censored and thus were only followed bytheir last visit.
Only three patients withdrew. They were considered fails. The small number makes it unlikely that they would have influenced the result. The authors state that “even with the exclusion of these three patients, there was no difference in the proportion of flares in the glucosamine and placebo groups.” |
| Selective reporting (reporting bias) | Low risk | A pre-specified protocol was not available, but all described outcomes are reported. Primary end-point of a disease flare was reported in Fig 2. Secondary outcomes all reported. |
| Other bias | Low risk | No conflict of interest werereported. The protocol appeared solid. |