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Acetazolamide versus placebo for cerebral oedema requiring dexamethasone in recurrent and/or progressive high-grade glioma: phase II randomised placebo-controlled double-blind study
  1. Meera R Agar1,2,
  2. Anna K Nowak3,4,
  3. Elizabeth J Hovey5,6,
  4. Elizabeth H Barnes7,
  5. John Simes7,8,
  6. Janette L Vardy9,10,
  7. Helen R Wheeler11,
  8. Benjamin Y Kong7,11,
  9. Robyn Leonard7,
  10. Merryn Hall7,
  11. Evonne Tim7,
  12. Desma Spyridopoulos7,
  13. Hao-Wen Sim7,8,
  14. Zarnie Lwin12,13,
  15. Anthony Dowling14,
  16. Rosemary Harrup15,
  17. Ross Jennens16,
  18. Ganessan Kichenadasse17,
  19. Tracey Dunlop18,
  20. Cecelia Gzell19 and
  21. Eng-Siew Koh6,20
  1. 1 Palliative Care, Liverpool Hospital, Liverpool, New South Wales, Australia
  2. 2 Health, University of Technology Sydney, Sydney, New South Wales, Australia
  3. 3 Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
  4. 4 Medical School, The University of Western Australia, Crawley, Western Australia, Australia
  5. 5 Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, New South Wales, Australia
  6. 6 Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
  7. 7 NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia
  8. 8 Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia
  9. 9 Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
  10. 10 Medical Oncology, Concord Repatriation General Hospital, Concord, New South Wales, Australia
  11. 11 Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
  12. 12 Medical Oncology, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
  13. 13 Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
  14. 14 Medical Oncology, St Vincent's Hospital Melbourne Pty Ltd, Fitzroy, Victoria, Australia
  15. 15 Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia
  16. 16 Medical Oncology, Epworth HealthCare, Richmond, Victoria, Australia
  17. 17 Flinders Centre for Innovation in Health Care, Flinders Medical Centre, Bedford Park, South Australia, Australia
  18. 18 Medical Oncology, St George Hospital, Kogarah, New South Wales, Australia
  19. 19 Genesis Care Pty Ltd, Darlinghurst, New South Wales, Australia
  20. 20 Radiation Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia
  1. Correspondence to Dr Meera R Agar, Palliative Care, Liverpool Hospital, Liverpool, New South Wales, Australia; meera.agar{at}


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.

  • brain
  • supportive care
  • quality of life

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Contributors MA, EHB, ES-K wrote the main manuscript text. AN, EJH, JS, JLV, HRW, H-WS, ZL, AD, RH, RJ, GK, TD, CG and E-SK collected data. EHB prepared all tables and figures. All authors reviewed the manuscript. ESK is responsible for the overall content as guarantor, had full access to the data and controlled the decision to publish.

  • Funding Cancer Australia Priority-Driven Collaborative Cancer Research Scheme (APP1098932); Perpetual Foundation (FR2014_0337).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.