Clinical trial NCT00367081: Treatment of Cerebral Toxoplasmosis in HIV/AIDS
Official title: Pyrimethamine Plus Sulfadiazine Versus Trimethoprim Plus Sulfamethoxazole for Treatment of Toxoplasmic Encephalitis in AIDS Patients: A Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Toxoplasmic Encephalitis
AIDS
Keywords: Toxoplasmic Encephalitis
AIDS
Lead sponsor: Department of Medical Services Ministry of Public Health of Thailand
Sponsor class: OTHER_GOV
Collaborators: name: Chiang Mai University
First posted: 2006-08-22
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Neurological manifestations of Cerebral toxoplasmosis or Toxoplasmic encephalitis (TE) in most advance stage HIV infected patients composed of fever, headache, alteration of consciousness with focal neurological signs/symptoms such as include hemiparesis, cranial nerve palsies, and ataxia. Generalised convulsions, in ¾ of patients. Moreover meningeal irritation sign or herniation sign may be presented as life threatening condition

Detailed description: Background: Toxoplasmic encephalitis (TE), caused by Toxoplasma gondii, is common in AIDS patients. TE can result in tissue destruction via massive inflammation and brain abscess formation. METHODS: Randomized controlled trials were performed in AIDS patients to assess which drug regimen was optimally effective for the treatment of TE. AIDS patients with TE were randomly divided into 3 groups that received a 6-week course of either pyrimethamine (50 mg/ day or 100 mg/day) plus sulfadiazine (4 g/day) and folinic acid (25 mg/day) or trimethoprim (10 mg/kg/day) plus sulfamethoxazole (50 mg/kg/day) (TMP-SMX), and results were evaluated with respect to clinical response, mortality, morbidity, and serious adverse events. The primary outcome was defined as death in the first 6-week period. The secondary outcome was successful treatment within 6 weeks without severe adverse events, bone marrow suppression, drug-induced rash, or any other event that caused a change in the treatment regimen. RESULTS: The results from this study showed that in AIDS patients, TE was most successfully treated with the combination of pyrimethamine (50 mg/day) plus sulfadiazidine (4 g/day) and folinic acid (25 mg/day); failure rates were not significantly different among the 3 treatment groups. Conclusions: Available data suggest that of the currently available options, treatment of TE with pyrimethamine at 50 mg/day plus sulfadiazidine at 4 g/day provides the best primary outcome for AIDS patients with TE; however, because this study was terminated prematurely, we suggest that treatment with intravenous TMP-SMX be further evaluated to determine its efficacy.

Eligibility criteria: Inclusion Criteria:

* AIDS
* Age \> 16 years
* Clinical Diagnosis of Cerebral toxoplasmosis, Toxoplasmic encephalitis
* Positive serum titer for Toxoplasma gondii or Positive CSF titer for Toxoplasma gondii after treatment within 2 weeks
* CT scan suspected toxoplasmosis, ring enhancing lesion
* CD4\<200

Exclusion Criteria:

* Sulfa drugs allergy
* positive lymphoma cell cytology in CSF
* no informed consent by patients or first degreee relatives
* CD4 \>200

Primary outcomes:
measure: Survival rate
Secondary outcomes:
measure: Complete medication rate
Other outcomes:
Locations:
city: Chiang Mai
country: Thailand
facility: Chiang Mai University hospital (2003-2004)
Study officials:
affiliation: Department of Medical Services Ministry of Public Health of Thailand
name: Subsai Kongsaengdao, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kongsaengdao S, Samintarapanya K, Oranratnachai K, Prapakarn W, Apichartpiyakul C. Randomized controlled trial of pyrimethamine plus sulfadiazine versus trimethoprim plus sulfamethoxazole for treatment of toxoplasmic encephalitis in AIDS patients. J Int Assoc Physicians AIDS Care (Chic). 2008 Jan-Feb;7(1):11-6. doi: 10.1177/1545109707301244. Epub 2007 May 21.