Clinical trial NCT04341155: Dexamethasone for Cerebral Toxoplasmosis
Official title: Adjunctive Dexamethasone for Cerebral Toxoplasmosis: a Double-blinded Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Toxoplasmosis, Cerebral
Lead sponsor: Universitas Padjadjaran
Sponsor class: OTHER
First posted: 2020-04-10
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or above.
2. Clinical signs and symptoms compatible to cerebral toxoplasmosis
3. Serology HIV positive
4. Immunoglobulin G anti-toxoplasma titre is positive
5. One or more mass lesions on the neuroradiological finding
6. None or less than 3 days of dexamethasone therapy taken
7. Written informed consent from the patients or from close relatives of the patient if the patient is unconscious.

Exclusion Criteria:

1. History of anti-toxoplasmosis administrattion for more than 5 days before recruitment
2. Hypersensitivity or other contraindication to dexamethasone
3. Pregnancy

Primary outcomes:
measure: Mortality
timeFrame: 90 days
Secondary outcomes:
measure: Number of participants with grade 3 and 4 and serious adverse events related to study drug
timeFrame: 7 days
measure: Changes in consciousness
timeFrame: 14 days
measure: Neurological response (1)
timeFrame: up to 90 days
measure: Neurological response (2)
timeFrame: up to 90 days
measure: Cognitive function (1)
timeFrame: up to 90 days
measure: Cognitive function (2)
timeFrame: up to 90 days
measure: Neuroradiological response
timeFrame: 90 days
Other outcomes:
Locations:
city: Bandung
country: Indonesia
facility: Hasan Sadikin General Hospital
state: Jawa Barat
Study officials:
affiliation: Faculty of Medicine Universitas Padjadjaran Bandung
name: Sofiati Dian, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
References: