TerminatedPhase 2ACTRN12615001072505

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

Sponsor

The University of Sydney

Enrollment

84 participants

Start Date

Jul 19, 2016

Study Type

Interventional

Conditions

Cerebral Oedema in recurrent, progressive and/or persistent High Grade Glioma

Summary

This study investigates whether addition of the drug acetazolamide to a dexamethasone treatment for controlling raised intracranial pressure symptoms, related to high grade glioma brain tumour (such as headache, nausea and vomiting), will allow the dexamethasone dosage to be reduced, and whether this leads to less dexamethasone-related side-effects. Who is it for? You can join this study if you are required to restart or increase a dexamethasone treatment to control recurrent or increased symptoms of intracranial pressure, that may be related to your brain tumour, high grade glioma. Study details: If you like to join this study you will first be screened by your specialist to see if you meet the eligibility criteria to participate in this study. If you are deemed eligible to participate you will be randomly (by chance) assigned to one of two possible treatment groups: Group 1 will receive 1 tablet of 250mg acetazolamide twice per day for 8 weeks, in addition to the dexamethasone treatment. Group 2 will receive 1 tablet of placebo twice per day for 8 weeks, in addition to the dexamethasone treatment. Your chance to receive the group 1 treatment is equally high as to receive the group 2 treatment. You cannot choose to which group you are assigned and both you and your doctor will not know which treatment you received until the study is finished. Participants will be asked to attend clinic visits every 2 weeks during the treatment period and then 1 more time (about 1 month after having received the last treatment). During these visits the specialist will assess your physical and mental health, and ask you about your well-being. Participants will also be asked to undergo tests and procedures, such as blood testing, scans, and questionnaire completion.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria17

Adults aged greater than or equal to 18 years;
Pathological diagnosis of HGG NOTE: HGG includes glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ependymoma, anaplastic oligoastrocytoma;
Clinically or radiologically diagnosed progressive, recurrent and/or persistent residual disease;
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);
Current dexamethasone dose of a minimum of 4mg per day;
Stable dexamethasone dose (after dose increase or recommencement) for at least 72 hours before randomisation;
Baseline Karnofsky Performance Status of greater than or equal to 40 at baseline;
Ability to swallow oral medication;
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);
Adequate renal function (creatinine clearance > 50 ml/min measured using Cockroft-Gault);
Adequate haematological function (Neutrophils greater than or equal to 1.0x10^9 cells/L, Platelets greater than or equal to 100x10^9 cells/L)
Serum sodium greater than or equal to 130 mmol/L;
Serum potassium between 3-5mmol/L
Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
Ability to complete patient-reported measures (in English), or if unable a caregiver who can complete caregiver questionnaires;
Signed, written informed consent;
Concurrent salvage single or multiple agent chemotherapy including temozolomide (any schedule), carboplatin, a nitrosurea (e.g. CCNU), or etoposide, is permissible.

Exclusion Criteria13

Confirmed allergy to sulphur (sulfonamides) (acetazolamide is a sulfonamide derivative and cross sensitivity between acetazolamide, sulfonamides and other sulfonamide derivatives can occur);
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;
No further neurosurgical procedure planned for the next 8 weeks;
Pre-existing metabolic acidosis (pH < 7.35 and bicarbonate levels <24 mmol/l);
History of nephrolithiasis;
Systolic Blood Pressure < 100 mmHg;
Chronic liver disease (Childs class A or above);
Systemic corticosteroid use (dexamethasone or prednisone/prednisolone) required for any indication other than cerebral oedema;
Current oral acetazolamide use for any indication;
Current bevacizumab therapy or use in prior 4 weeks;
Current salvage re-irradiation;
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;
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.

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Interventions

Eligible participants will be randomised to the study in 1:1 ratio to either study treatment or control. The study treatment group will receive 1 tablet of 250 mg acetazolamide twice per day for 8

Eligible participants will be randomised to the study in 1:1 ratio to either study treatment or control. The study treatment group will receive 1 tablet of 250 mg acetazolamide twice per day for 8 weeks. The placebo group will receive 1 tablet of placebo twice per day for 8 weeks. Drug accountability will be checked at each visit with bottle counts.