Acetazolamide versus placebo for cerebral oedema requiring dexamethasone in recurrent and/or progressive high-grade glioma: phase II randomised placebo-controlled double-blind study.

Agar, MR; Nowak, AK; Hovey, EJ; Barnes, EH; Simes, J; Vardy, JL; Wheeler, HR; Kong, BY; Leonard, R; Hall, M; Tim, E; Spyridopoulos, D; Sim, H-W; Lwin, Z; Dowling, A; Harrup, R; Jennens, R; Kichenadasse, G; Dunlop, T; Gzell, C; Koh, E-S

Acetazolamide versus placebo for cerebral oedema requiring dexamethasone in recurrent and/or progressive high-grade glioma: phase II randomised placebo-controlled double-blind study.

Agar, MR Nowak, AK Hovey, EJ Barnes, EH Simes, J Vardy, JL Wheeler, HR Kong, BY Leonard, R Hall, M Tim, E Spyridopoulos, D Sim, H-W Lwin, Z Dowling, A Harrup, R Jennens, R Kichenadasse, G Dunlop, T Gzell, C Koh, E-S

Permalink

Publisher:: BMJ
Publication Type:: Journal Article
Citation:: BMJ Support Palliat Care, 2023, 13, (3), pp. 354-362
Issue Date:: 2023-09

Closed Access

	Filename	Description	Size
	354.full.pdf		763.7 kB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Agar, MR
dc.contributor.author	Nowak, AK
dc.contributor.author	Hovey, EJ
dc.contributor.author	Barnes, EH
dc.contributor.author	Simes, J
dc.contributor.author	Vardy, JL
dc.contributor.author	Wheeler, HR
dc.contributor.author	Kong, BY
dc.contributor.author	Leonard, R
dc.contributor.author	Hall, M
dc.contributor.author	Tim, E
dc.contributor.author	Spyridopoulos, D
dc.contributor.author	Sim, H-W
dc.contributor.author	Lwin, Z
dc.contributor.author	Dowling, A
dc.contributor.author	Harrup, R
dc.contributor.author	Jennens, R
dc.contributor.author	Kichenadasse, G
dc.contributor.author	Dunlop, T
dc.contributor.author	Gzell, C
dc.contributor.author	Koh, E-S
dc.date.accessioned	2023-09-01T06:09:20Z
dc.date.available	2023-01-23
dc.date.available	2023-09-01T06:09:20Z
dc.date.issued	2023-09
dc.identifier.citation	BMJ Support Palliat Care, 2023, 13, (3), pp. 354-362
dc.identifier.issn	2045-435X
dc.identifier.issn	2045-4368
dc.identifier.uri	http://hdl.handle.net/10453/171876
dc.description.abstract	OBJECTIVES: Symptoms of raised intracranial pressure (ICP) in recurrent high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on ICP symptoms. Acetazolamide reduces ICP when used in other clinical non-cancer settings. The aim of the study was to explore whether the addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent HGG. METHODS: Participants had recurrent HGG with any of dexamethasone recommencement, dose increase or dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide or placebo for 8 weeks. Standardised protocols were used for dexamethasone dosing, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stable Karnofsky Performance Status Secondary endpoints included toxicity and feasibility. RESULTS: Thirty participants (15 per group) were enrolled (mean age 58 years) from seven Australian sites. The mean baseline dexamethasone dose was 6.2 mg. Mean duration on study treatment was 38 days (placebo group) and 31 days (acetazolamide group) with nine participants (30%) completing all study treatments (six placebo, three acetazolamide). Study withdrawal was due to adverse events (n=6; one placebo, five acetazolamide) and disease progression (n=6 (three per arm)). Four participants (13%) (two per arm) were stable responders. Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: five participants (33%), six events, two related). CONCLUSIONS: The study closed early due to poor accrual and increasing availability of bevacizumab. The addition of acetazolamide did not facilitate dexamethasone reduction. TRIAL REGISTRATION NUMBER: ACTRN12615001072505.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	BMJ
dc.relation.ispartof	BMJ Support Palliat Care
dc.relation.isbasedon	10.1136/spcare-2022-004119
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1110 Nursing, 1117 Public Health and Health Services
dc.subject.classification	4203 Health services and systems
dc.subject.classification	4205 Nursing
dc.subject.mesh	Humans
dc.subject.mesh	Middle Aged
dc.subject.mesh	Acetazolamide
dc.subject.mesh	Brain Edema
dc.subject.mesh	Bevacizumab
dc.subject.mesh	Double-Blind Method
dc.subject.mesh	Neoplasm Recurrence, Local
dc.subject.mesh	Australia
dc.subject.mesh	Glioma
dc.subject.mesh	Dexamethasone
dc.subject.mesh	Humans
dc.subject.mesh	Glioma
dc.subject.mesh	Neoplasm Recurrence, Local
dc.subject.mesh	Brain Edema
dc.subject.mesh	Acetazolamide
dc.subject.mesh	Dexamethasone
dc.subject.mesh	Double-Blind Method
dc.subject.mesh	Middle Aged
dc.subject.mesh	Australia
dc.subject.mesh	Bevacizumab
dc.subject.mesh	Humans
dc.subject.mesh	Middle Aged
dc.subject.mesh	Acetazolamide
dc.subject.mesh	Brain Edema
dc.subject.mesh	Bevacizumab
dc.subject.mesh	Double-Blind Method
dc.subject.mesh	Neoplasm Recurrence, Local
dc.subject.mesh	Australia
dc.subject.mesh	Glioma
dc.subject.mesh	Dexamethasone
dc.title	Acetazolamide versus placebo for cerebral oedema requiring dexamethasone in recurrent and/or progressive high-grade glioma: phase II randomised placebo-controlled double-blind study.
dc.type	Journal Article
utslib.citation.volume	13
utslib.location.activity	England
utslib.for	1110 Nursing
utslib.for	1117 Public Health and Health Services
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/IMPACCT
utslib.copyright.status	closed_access	*
dc.date.updated	2023-09-01T06:09:18Z
pubs.issue	3
pubs.publication-status	Published
pubs.volume	13
utslib.citation.issue	3

Abstract:

OBJECTIVES: Symptoms of raised intracranial pressure (ICP) in recurrent high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on ICP symptoms. Acetazolamide reduces ICP when used in other clinical non-cancer settings. The aim of the study was to explore whether the addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent HGG. METHODS: Participants had recurrent HGG with any of dexamethasone recommencement, dose increase or dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide or placebo for 8 weeks. Standardised protocols were used for dexamethasone dosing, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stable Karnofsky Performance Status Secondary endpoints included toxicity and feasibility. RESULTS: Thirty participants (15 per group) were enrolled (mean age 58 years) from seven Australian sites. The mean baseline dexamethasone dose was 6.2 mg. Mean duration on study treatment was 38 days (placebo group) and 31 days (acetazolamide group) with nine participants (30%) completing all study treatments (six placebo, three acetazolamide). Study withdrawal was due to adverse events (n=6; one placebo, five acetazolamide) and disease progression (n=6 (three per arm)). Four participants (13%) (two per arm) were stable responders. Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: five participants (33%), six events, two related). CONCLUSIONS: The study closed early due to poor accrual and increasing availability of bevacizumab. The addition of acetazolamide did not facilitate dexamethasone reduction. TRIAL REGISTRATION NUMBER: ACTRN12615001072505.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/171876