Dexamethasone for Cerebral Toxoplasmosis

Toxoplasmosis, Cerebral Clinical Trial

— De-Tox  

Official title:

Adjunctive Dexamethasone for Cerebral Toxoplasmosis: a Double-blinded Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04341155
• Other study ID #: TX-202003.01
• Status: Recruiting
• Phase: Phase 2
• Start date: April 16, 2021
• Est. completion date: July 2024

Study information

• Verified date: November 2023
• Source: Universitas Padjadjaran
• Contact: Ahmad R Ganiem, M.D., PhD
• Phone: +62 878 2288 3773
• Email: rizalbdg[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 138
• Est. completion date: July 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Toxoplasmosis
• Toxoplasmosis, Cerebral

Intervention

Drug:
• Dexamethasone
Patients in experimental arms will receive i.v. dexamethasone 20 mg (4 ampules = 20mL) for 7 days
• Placebo
Patients in placebo arms will receive 20 mL normal saline intravenously for 7 days

Locations

Country	Name	City	State
Indonesia	Hasan Sadikin General Hospital	Bandung	Jawa Barat

Sponsors (1)

Lead Sponsor	Collaborator
Universitas Padjadjaran

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	Determined by the time from randomization to death (in days)	90 days
Secondary	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.	7 days
Secondary	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	14 days
Secondary	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.	up to 90 days
Secondary	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.	up to 90 days
Secondary	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	up to 90 days
Secondary	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	up to 90 days
Secondary	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	90 days