Toxoplasma gondii infects over one third of the global human population. Cerebral toxoplasmosis is the most common opportunistic infection in HIV patients resulting in up to 50% of mortality with proper treatment and 80% without it. The fatality mainly due to the brain edema resulted from the mass effect lesion. In addition of anti toxoplasmosis given, adjunctive therapy such as steroid is recommended in order to reduce brain edema, but the dose and duration of administration in cerebral toxoplasmosis has not been evaluated in a clinical trial. Adjunctive therapy given in cerebral toxoplasmosis patients still remains unclear. Moreover, its safety in immunodeficiency cases is still debatable.
Steroid produces a raising expression of anti inflammation genes (NF-κB, IκB-α and antagonist receptor IL-1) and inhibits pro inflammation cytokines ( TNF-α and IL-1β). It also works as anti edema by correcting the disrupted blood brain barrier during infection process. Dexamethasone is considered to be chosen in this clinical trial due to the long half life among steroids, the strongest glucocorticoid effect comparing other steroids, and easily prepared and used on daily practice. There are limited data from using adjunctive steroid for treatment of HIV-associated with cerebral toxoplasmosis. Previous study in France published in 2012 showed steroid did not give any significant improvement for patients' neurological outcome and did not worsen patients' condition such as getting nosocomial infection. Meanwhile comparing previous study by Arens et. al in 2007, there was an increasing mortality rate on adjunctive steroid used in cerebral toxoplasmosis patients. As result of limited data, our trial is looked forward to answer about the efficacy of dexamethasone treatment in reducing mortality rate of cerebral toxoplasmosis patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
138
Patients in experimental arms will receive i.v. dexamethasone 20 mg (4 ampules = 20mL) for 7 days
Patients in placebo arms will receive 20 mL normal saline intravenously for 7 days
Hasan Sadikin General Hospital
Bandung, West Java, Indonesia
RECRUITINGMortality
Determined by the time from randomization to death (in days)
Time frame: 90 days
Number of participants with grade 3 and 4 and serious adverse events related to study drug
Signs and symptoms of adverse event related to study drug including hypersensitivity, GI upset, respiratory, skin, musculoskeletal problems, vertigo, and electrolyte imbalance will be assessed daily for 7 days since the first administration of study drugs.
Time frame: 7 days
Changes in consciousness
Glasgow Coma Scale (GCS) will be used to quantify the level of consciousness. GCS is a continuous scale ranging from 3 - 15 with higher scores represent better outcome GCS will be recorded every day until day 14 of hospitalization
Time frame: 14 days
Neurological response (1)
Neurological responses that show both improvement (e.g. regaining consciousness) and worsening (i.e. decreasing of consciousness, development of new neurological deficits) will be measured and recorded at days 3, 7, 30, 60 and 90. Neurological response will be measured by serial assessments of Glasgow Outcome Scale (GOS). GOS is a scale that measures objective degree of recovery. It has 6 degrees of measurement ranging from 0 to 5, with 0 equals death and 5 full recovery.
Time frame: up to 90 days
Neurological response (2)
Neurological responses that show both improvement (e.g. regaining consciousness) and worsening (i.e. decreasing of consciousness, development of new neurological deficits) will be measured and recorded at days 3, 7, 30, 60 and 90. Second neurological response measurement will be using serial assessments of Modified Rankin Scale (mRS). The modified Rankin Scale (mRS) is commonly used for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0 to 6, with 0 equals to perfect health without symptoms, and 6 equals to death; i.e. the higher the score, the worse the outcome.
Time frame: up to 90 days
Cognitive function (1)
Cognitive function will be measured by using Mini Mental State Examination (MMSE) as early as the subjects regain consciousness and at day 7, 30 and 90. MMSE is a continuous scale with values from 0 to 30, and considered normal if the value is more than or equal to 28
Time frame: up to 90 days
Cognitive function (2)
The second cognitive function measurement will be using Montreal Cognitive Assessment Indonesian version (MoCA INA) as early as the subjects regain consciousness and at day 7, 30 and 90. MoCA-INA is a continuous scale with values from 0 to 30, and considered normal if the value is more than or equal to 26
Time frame: up to 90 days
Neuroradiological response
Change in brain oedema or development of any CT-scan abnormalities related to cerebral toxoplasmosis will documented by performing and comparing two series of CT-scan with contrast administration that will be done within the first 3 days and at day 90 (+/- 7 days) after randomisation
Time frame: 90 days
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