TY - JOUR
T1 - Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage
T2 - a statistical analysis plan for the DRAIN randomised clinical trial
AU - Capion, Tenna
AU - Lilja-Cyron, Alexander
AU - Juhler, Marianne
AU - Møller, Kirsten
AU - Sorteberg, Angelika
AU - Rønning, Pål André
AU - Poulsen, Frantz Rom
AU - Wismann, Joakim
AU - Schack, Anders Emil
AU - Ravlo, Celina
AU - Isaksen, Jørgen
AU - Lindschou, Jane
AU - Gluud, Christian
AU - Mathiesen, Tiit
AU - Olsen, Markus Harboe
N1 - © 2024. The Author(s).
PY - 2024/7/15
Y1 - 2024/7/15
N2 - 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 a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding 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. Registered on May 13, 2019.
AB - 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 a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding 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. Registered on May 13, 2019.
KW - Humans
KW - Subarachnoid Hemorrhage/complications
KW - Hydrocephalus/etiology
KW - Randomized Controlled Trials as Topic
KW - Drainage/adverse effects
KW - Treatment Outcome
KW - Time Factors
KW - Multicenter Studies as Topic
KW - Data Interpretation, Statistical
KW - Quality of Life
KW - Denmark
KW - Ventriculoperitoneal Shunt/adverse effects
UR - http://www.scopus.com/inward/record.url?scp=85198668641&partnerID=8YFLogxK
U2 - 10.1186/s13063-024-08305-4
DO - 10.1186/s13063-024-08305-4
M3 - Journal article
C2 - 39010208
SN - 1745-6215
VL - 25
SP - 479
JO - Trials
JF - Trials
IS - 1
M1 - 479
ER -