When and how should we cluster and cross over: methodological and ethical issues (letter 2)

Lee, Shun Fu; Bangdiwala, Shrikant I.; Spence, Jessica; Connolly, Stuart J.

doi:10.1007/s12630-018-1238-4

Cited by 2 publications

(2 citation statements)

References 6 publications

(4 reference statements)

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“…Seventy-two randomized participants are required for this design to detect a clinically meaningful reduction in change in IRLS of 3, 27 assuming a standard deviation of 6 in change in IRLS 15 with repeated measures at 3 and 4 weeks of every crossover period with a correlation in repeated measures of 0.88, 13 an interperiod correlation of 0.2, a 2-sided type I error of 2.5%, and a power of 80%, assuming a 10% loss to follow-up. The interperiod correlation of 0.2 was assumed based on experiences with previous crossover trials 28 and a 10% loss to follow-up based on previous trials of RLS in ESKD. 12 Participants who do not complete more than 2 crossover periods will be replaced (but their data retained) until a maximum sample size of 80 patients is met.…”

Section: Statistical Considerationsmentioning

confidence: 99%

The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) Trial: A Protocol for a Randomized, Crossover, Placebo-Controlled Blinded Trial

Collister

Pohl

Herrington³

et al. 2020

Can J Kidney Health Dis

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Background: Restless legs syndrome (RLS) affects approximately 30% of patients with end-stage kidney disease and is associated with impaired sleep and health-related quality of life. Medications used to treat RLS in patients receiving dialysis may have an increased risk of adverse events with dose titration, and residual RLS symptoms are common despite the use of effective treatments. Randomized controlled trials of monotherapy and combination pharmacologic therapy for RLS in hemodialysis are needed. Objective: To perform a randomized, crossover, placebo-controlled blinded trial of pharmacologic therapy for RLS in hemodialysis. Design/setting: The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) trial is a randomized, crossover, placebo-controlled blinded trial of fixed low-dose pharmacologic therapy in patients receiving hemodialysis in 10 centers across Canada. It uses patient partners in its design, conduct, and reporting. Participants: Adults receiving thrice-weekly hemodialysis for at least 3 months with RLS of at least mild symptoms defined International Restless Legs Syndrome Study Group Rating Scale (IRLS) of 10 or more will enter a double placebo run-in period to exclude nonadherent participants and those unable to tolerate double placebo. Seventy-two participants who completed the run-in period will be randomized to 1 of 8 treatment sequences based on modeling with 4 treatment periods. Methods: Each treatment period lasts 4 weeks and consists of ropinirole 0.5 mg daily and gabapentin 100 mg daily, both together or neither with a double dummy placebo control for each treatment. The primary outcome is the difference in change scores of the IRLS between study treatments. Secondary outcomes are the differences in change scores of the Restless Legs Syndrome-6 Scale, patient global impression, 5-level EQ-5D version, and safety outcomes. Results: This randomized, crossover, placebo-controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination of ropinirole and gabapentin in patients receiving hemodialysis with RLS. Limitations: Patients with chronic kidney disease not on dialysis, kidney transplant recipients and those receiving peritoneal dialysis or home hemodialysis are not included. The intervention’s long term safety and efficacy including the risk of augmentation is not captured. Conclusion: This randomized crossover placebo controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination ropinirole and gabapentin in patients receiving hemodialysis with RLS. Trial Registration: ClinicalTrials.gov (NCT03806530)

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Section: Statistical Considerationsmentioning

confidence: 99%

The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) Trial: A Protocol for a Randomized, Crossover, Placebo-Controlled Blinded Trial

Collister

Pohl

Herrington³

et al. 2020

Can J Kidney Health Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…2 Lee et al agree that we make ''correct statements about methodological concerns for cluster crossover trials in general.'' 3 They agree that these include increased risks of bias, limited external validity, imbalances in baseline characteristics, and carry-over and period effects, and they explain how each will be addressed in the full-scale B-Free trial. 3 We note that Lee et al make no effort to defend the original thesis that cluster crossover trials are generally the preferred design to evaluate questions of effectiveness.…”

Section: To the Editormentioning

confidence: 99%

In reply: When and how should we cluster and cross over: methodological and ethical issues (letters 1 and 2)

Goldstein

Giraudeau

Weijer

et al. 2018

Can J Anesth/J Can Anesth

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When and how should we cluster and cross over: methodological and ethical issues (letter 2)

Cited by 2 publications

References 6 publications

The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) Trial: A Protocol for a Randomized, Crossover, Placebo-Controlled Blinded Trial

The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) Trial: A Protocol for a Randomized, Crossover, Placebo-Controlled Blinded Trial

In reply: When and how should we cluster and cross over: methodological and ethical issues (letters 1 and 2)

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