A Phase II randomised placebo-controlled, double blind, multisite study of Acetazolamide versus placebo for management of cerebral oedema in recurrent and/or progressive High Grade Glioma requiring treatment with Dexamethasone – The ACED trial

Phase 2

• Conditions: Cerebral Oedema in recurrent, progressive and/or persistent High Grade Glioma; Cancer - Brain

• Registration Number: ACTRN12615001072505
• Lead Sponsor: The University of Sydney

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-10-13
• Last Update Posted: 10 March 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1) Adults aged greater than or equal to 18 years;
2) Pathological diagnosis of HGG NOTE: HGG includes glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ependymoma, anaplastic oligoastrocytoma;
3) Clinically or radiologically diagnosed progressive, recurrent and/or persistent residual disease;
4) Recommencement of dexamethasone, dexamethasone dose increase, or dexamethasone dependent (unable to reduce below 4mg or cease over 8 weeks); for the management of raised ICP (regardless of aetiology);
5) Current dexamethasone dose of a minimum of 4mg per day;
6) Stable dexamethasone dose (after dose increase or recommencement) for at least 72 hours before randomisation;
7) Baseline Karnofsky Performance Status of greater than or equal to 40 at baseline;
8) Ability to swallow oral medication;
9) Adequate liver function (Bilirubin less than or equal to 2.5 times upper limit of normal; Alkaline phosphatase, aspartate transaminase and alanine transaminase less than or equal to 3 times upper limit of normal);
10) Adequate renal function (creatinine clearance > 50 ml/min measured using Cockroft-Gault);
11. Adequate haematological function (Neutrophils greater than or equal to 1.0x10^9 cells/L, Platelets greater than or equal to 100x10^9 cells/L)
12. Serum sodium greater than or equal to 130 mmol/L;
13. Serum potassium between 3-5mmol/L
14. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
15. Ability to complete patient-reported measures (in English), or if unable a caregiver who can complete caregiver questionnaires;
16. Signed, written informed consent;
17. Concurrent salvage single or multiple agent chemotherapy including temozolomide (any schedule), carboplatin, a nitrosurea (e.g. CCNU), or etoposide, is permissible.

Exclusion Criteria

1) Confirmed allergy to sulphur (sulfonamides) (acetazolamide is a sulfonamide derivative and cross sensitivity between acetazolamide, sulfonamides and other sulfonamide derivatives can occur);
2) Have had any surgery, open biopsy, intracranial biopsy, ventriculoperitoneal shunt or significant traumatic injury within 2 weeks prior to start of treatment on this study or who have not recovered from side effects of such therapy;
3) No further neurosurgical procedure planned for the next 8 weeks;
4) Pre-existing metabolic acidosis (pH < 7.35 and bicarbonate levels <24 mmol/l);
5) History of nephrolithiasis;
6) Systolic Blood Pressure < 100 mmHg;
7) Chronic liver disease (Childs class A or above);
8) Systemic corticosteroid use (dexamethasone or prednisone/prednisolone) required for any indication other than cerebral oedema;
9) Current oral acetazolamide use for any indication;
10) Current bevacizumab therapy or use in prior 4 weeks;
11) Current salvage re-irradiation;
12) Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;
13) Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 10 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Composite endpoint of dexamethasone dose reduction and stability of neurological function, determined by: <br><br>1) At least 50% corticosteroid dose reduction from baseline (baseline dosage is considered the stable dose for at least 3 days prior to randomisation), achieved within 28 days from randomisation and maintained it for > 7 days<br><br>AND<br><br>2) Without deterioration in neurological function (deterioration is defined as a decrease in Karnofsky Performance Status of 20 points or more)[Day 36 from randomisation]