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Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial

a statistical analysis plan for the DRAIN randomised clinical trial
Authors: Tenna Capion; Alexander Lilja-Cyron; Marianne Juhler; Kirsten Møller; Angelika Sorteberg; Pål André Rønning; Frantz Rom Poulsen; +8 Authors

Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial

Abstract

Abstract Background: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections. Methods: DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excl. mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%) 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded Steering Group will formulate two abstracts. Conclusion: We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility. Trial registration: ClinicalTrials.gov identifier: NCT03948256

Keywords

Statistical analysis plan, Medicine (General), Data Interpretation, Time Factors, Drainage/adverse effects, Denmark, 610, Weaning, Ventriculoperitoneal Shunt, Randomised clinical trial, R5-920, Hydrocephalus/etiology, Humans, Multicenter Studies as Topic, Aneurysmal subarachnoid haemorrhage, Randomized Controlled Trials as Topic, Methodology, Ventriculoperitoneal Shunt/adverse effects, Statistical, Subarachnoid Hemorrhage, Aneurysm, Treatment Outcome, Data Interpretation, Statistical, Subarachnoid Hemorrhage/complications, Quality of Life, Drainage, External ventricular drain, Hydrocephalus

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
Green
gold