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Dexamethasone for Cerebral Toxoplasmosis (De-Tox)

Primary Purpose

Toxoplasmosis, Cerebral

Status
Recruiting
Phase
Phase 2
Locations
Indonesia
Study Type
Interventional
Intervention
Dexamethasone
Placebo
Sponsored by
Universitas Padjadjaran
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Toxoplasmosis, Cerebral

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hasan Sadikin General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Dexamethasone

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Mortality
Determined by the time from randomization to death (in days)

Secondary Outcome Measures

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.
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
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.
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.
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
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
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

Full Information

First Posted
March 31, 2020
Last Updated
November 14, 2022
Sponsor
Universitas Padjadjaran
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1. Study Identification

Unique Protocol Identification Number
NCT04341155
Brief Title
Dexamethasone for Cerebral Toxoplasmosis
Acronym
De-Tox
Official Title
Adjunctive Dexamethasone for Cerebral Toxoplasmosis: a Double-blinded Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 16, 2021 (Actual)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitas Padjadjaran

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 easy 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Toxoplasmosis, Cerebral

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
138 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dexamethasone
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Dexamethasone - Phapros
Intervention Description
Patients in experimental arms will receive i.v. dexamethasone 20 mg (4 ampules = 20mL) for 7 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal Saline 0,9% - B Braun
Intervention Description
Patients in placebo arms will receive 20 mL normal saline intravenously for 7 days
Primary Outcome Measure Information:
Title
Mortality
Description
Determined by the time from randomization to death (in days)
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Number of participants with grade 3 and 4 and serious adverse events related to study drug
Description
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
Title
Changes in consciousness
Description
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
Title
Neurological response (1)
Description
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
Title
Neurological response (2)
Description
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
Title
Cognitive function (1)
Description
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
Title
Cognitive function (2)
Description
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
Title
Neuroradiological response
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 years or above. Clinical signs and symptoms compatible to cerebral toxoplasmosis Serology HIV positive Immunoglobulin G anti-toxoplasma titre is positive One or more mass lesions on the neuroradiological finding None or less than 3 days of dexamethasone therapy taken Written informed consent from the patients or from close relatives of the patient if the patient is unconscious. Exclusion Criteria: History of anti-toxoplasmosis administrattion for more than 5 days before recruitment Hypersensitivity or other contraindication to dexamethasone Pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ahmad R Ganiem, M.D., PhD
Phone
+62 878 2288 3773
Email
rizalbdg@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sofiati Dian, M.D., PhD
Phone
+62 812 2119 519
Email
sofiatidian@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sofiati Dian, M.D., PhD
Organizational Affiliation
Faculty of Medicine Universitas Padjadjaran Bandung
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hasan Sadikin General Hospital
City
Bandung
State/Province
Jawa Barat
ZIP/Postal Code
40161
Country
Indonesia
Individual Site Status
Recruiting

12. IPD Sharing Statement

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Dexamethasone for Cerebral Toxoplasmosis

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