Dexamethasone for Cerebral Toxoplasmosis (De-Tox)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Toxoplasmosis, Cerebral
• Intervention / Treatment: Drug: Dexamethasone; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ahmad R Ganiem, M.D., PhD; Phone Number: +62 878 2288 3773; Email: rizalbdg@gmail.com
• Study Contact Backup: Name: Sofiati Dian, M.D., PhD; Phone Number: +62 812 2119 519; Email: sofiatidian@gmail.com

Study Locations

• Indonesia
  • Jawa Barat
    • Bandung, Jawa Barat, Indonesia, 40161
      • Recruiting
      • Hasan Sadikin General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dexamethasone; Sixty nine patients will be administered randomly dexamethasone 20 mg IV for 7 days. Along with study drug or placebo, patients will receive standard anti toxoplasmosis (Oral pyrimethamine 150 or 200 mg (according to body weight) for three days continued by 50 or 75mg (according to body weight) per day or oral cotrimoxazole 2 x 1920 mg; oral clindamycin 600mg q.i.d) in accordance to national neurologist association guidelines.	Drug: Dexamethasone; Patients in experimental arms will receive i.v. dexamethasone 20 mg (4 ampules = 20mL) for 7 days; Other Names: Dexamethasone - Phapros
Placebo Comparator: Placebo; Sixty nine patients will be administered randomly Normal Saline 0,9% IV (4 cc) for 7 days. Along with study drug or placebo, patients will receive standard anti toxoplasmosis (Oral pyrimethamine 150 or 200 mg (according to body weight) for three days continued by 50 or 75mg (according to body weight) per day or oral cotrimoxazole 2 x 1920 mg; oral clindamycin 600mg q.i.d) in accordance to national neurologist association guidelines.	Drug: Placebo; Patients in placebo arms will receive 20 mL normal saline intravenously for 7 days; Other Names: Normal Saline 0,9% - B Braun

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Determined by the time from randomization to death (in days)	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Universitas Padjadjaran
• Investigators: Principal Investigator: Sofiati Dian, M.D., PhD, Faculty of Medicine Universitas Padjadjaran Bandung

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2021
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 7, 2020
• First Posted (Actual): April 10, 2020

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Parasitic Diseases; Coccidiosis; Protozoan Infections; Suppuration; Central Nervous System Parasitic Infections; Abscess; Brain Abscess; Central Nervous System Protozoal Infections; Toxoplasmosis; Toxoplasmosis, Cerebral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: TX-202003.01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No