Influence of Trimethoprim-Sulfamethoxazole for the Recurrence of Ocular Toxoplasmosis (ISROT)

This study has been completed.
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Joao Paulo Felix, University of Campinas, Brazil
ClinicalTrials.gov Identifier:
NCT01449877
First received: October 6, 2011
Last updated: July 10, 2016
Last verified: July 2016
  Purpose
The investigators study aims to determine the effect of prophylactic therapy with Trimethoprim-sulfamethoxazole on the recurrences of toxoplasma retinochoroiditis gondii. This is a randomized, double-masked, in patients with eye condition of acute Toxoplasma gondii retinochoroiditis. Volunteers will be recruited with a previous diagnosis of chorioretinitis presumed Toxoplasma gondii, which show active lesions compatible with recurrence. After the acute phase of treatment of all patients [1 tablet Trimethoprim-sulfamethoxazole (800/160mg) 12/12h during 45 days], the same Stratified by gender) will be randomized in a 1:1 ratio between the group 1 - TMP-SMZ (prophylactic treatment with trimethoprim-sulfamethoxazole 1 tablet every other day for 311 days) or group 2 - placebo (consisting of a placebo pill containing no active ingredient of similar appearance to trimethoprim-sulfamethoxazole, 1 tablet every other day for 311 days). The primary outcomes are incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 12, 36, 48, 60, 72, 84, 96, 108, and 120 months. Patients will be followed during the ten years in uveitis clinic at intervals defined as follows: return weekly for 4 weeks, then monthly for 2 months, then each 3 months for 9 months, and finally annually for 10 years.

Condition Intervention Phase
Ocular Toxoplasmosis
Drug: Trimethoprim-Sulfamethoxazole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Influence of Trimethoprim-sulfamethoxazole for the Recurrence of Retinochoroiditis Toxoplasma Gondii

Resource links provided by NLM:


Further study details as provided by University of Campinas, Brazil:

Primary Outcome Measures:
  • Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 12 months. [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 36 months. [ Time Frame: Three years ] [ Designated as safety issue: Yes ]
  • Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 48 months. [ Time Frame: Four years ] [ Designated as safety issue: Yes ]
  • Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 60 months. [ Time Frame: Five years ] [ Designated as safety issue: Yes ]
  • Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 72 months. [ Time Frame: Six years ] [ Designated as safety issue: Yes ]
  • Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 84 months. [ Time Frame: Seven years ] [ Designated as safety issue: Yes ]
  • Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 96 months. [ Time Frame: Eight years ] [ Designated as safety issue: Yes ]
  • Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 108 months. [ Time Frame: Nine years ] [ Designated as safety issue: Yes ]
  • Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 120 months. [ Time Frame: Ten years ] [ Designated as safety issue: Yes ]

Enrollment: 141
Study Start Date: October 2011
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Trimethoprim-Sulfamethoxazole
1 tablet every other day, morning.
Drug: Trimethoprim-Sulfamethoxazole
Sulfamethoxazole 800mg + Trimethoprim 160mg / tablet. In treatment of acute phase, 1 tablet 12/12h 45 days. After acute phase, 1 tablet every other day, morning, 311 days. Placebo tablet - Composition: starch. After acute phase, 1 tablet every other day, morning, 311 days.
Other Name: Sulfamethoxazole 800mg + Trimethoprim 160mg = Bactrim F.
Placebo Comparator: Starch tablet
1 starch tablet every other day, morning.
Drug: Trimethoprim-Sulfamethoxazole
Sulfamethoxazole 800mg + Trimethoprim 160mg / tablet. In treatment of acute phase, 1 tablet 12/12h 45 days. After acute phase, 1 tablet every other day, morning, 311 days. Placebo tablet - Composition: starch. After acute phase, 1 tablet every other day, morning, 311 days.
Other Name: Sulfamethoxazole 800mg + Trimethoprim 160mg = Bactrim F.

Detailed Description:
The protozoan Toxoplasma gondii is an obligate intracellular parasite, a common cause of intraocular inflammation in the world. The treatment of toxoplasmosis is the sulfonamide group of drugs, which acts on tachyzoites forms, no acting on bradyzoites, that grown from latent focus located on boards and are responsible for recurrence. The investigators study aims to determine the effect of prophylactic therapy with Trimethoprim-sulfamethoxazole on the recurrences of toxoplasma retinochoroiditis gondii. This is a randomized, double-masked, in patients with eye condition of acute Toxoplasma gondii retinochoroiditis. The study population consists of patients treated at Ophthalmology department, University of Campinas. They present symptoms compatible with a diagnosis of recurrent ocular toxoplasmosis. Volunteers will be recruited with a previous diagnosis of chorioretinitis presumed Toxoplasma gondii, which show active lesions compatible with recurrence. After the acute phase of treatment of all patients [1 tablet Trimethoprim-sulfamethoxazole (800/160mg) 12/12h during 45 days], the same Stratified by gender) will be randomized in a 1:1 ratio between the group 1 - TMP-SMZ (prophylactic treatment with trimethoprim-sulfamethoxazole 1 tablet every other day for 311 days) or group 2 - placebo (consisting of a placebo pill containing no active ingredient of similar appearance to trimethoprim-sulfamethoxazole, 1 tablet every other day for 311 days). The definition of a patient with recurrent episode of chorioretinitis Toxoplasmosis is the presence of old scars of chorioretinitis, associated with satellite active lesions chorioretinitis with positive IgG for toxoplasmosis. The new recurrence was treated with 1 tablet Trimethoprim-sulfamethoxazole (800/160mg) 12/12h during 45 days. The patients will be tested for visual acuity, examination biomicroscopy, tonometry, fundus photography and indirect ophthalmoscopy. In each study, patients will be randomized in blocks of four (two in group I and two Group II) with stratification by gender. The primary outcomes are incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 12, 36, 48, 60, 72, 84, 96, 108, and 120 months. It was planned a minimum sample of 140 patients (70 in group I and 70 in group II). Assuming an incidence of 6% recurrence in group A, this sample will have a 80% power to detect a difference of 18% between groups. The results of this analysis will be considered significant if p <0.05. The main variables are age, sex, presence of unilateral or bilateral eye injury, number of recurrences, number and location of lesions, and previous treatment for ocular toxoplasmosis. Patients will be followed during the ten years in uveitis clinic at intervals defined as follows: return weekly for 4 weeks, then monthly for 2 months, then each 3 months for 9 months, and finally annually for 10 years. Patients will be trained to return immediately if they have any of the following symptoms: decreased visual acuity, photophobia, floaters or ocular hyperemia. Adverse events will be monitored. The definition of a patient with a recurrent episode of chorioretinitis Toxoplasmosis is the presence of old scars of chorioretinitis, associated with active satellite lesions chorioretinitis with positive IgG for toxoplasmosis. To data collection, will be used semi-structured questionnaire, containing the patient record, age, gender, visual acuity by ETDRS chart, the affected eye and previous treatment for ocular toxoplasmosis.
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Positive IgG result for toxoplasmosis (IgG)
  • Ipsilateral scars of retina compatible with previous episode of toxoplasmosis retinochoroiditis
  • Unilateral active lesion of chorioretinitis

Exclusion Criteria:

  • Under 18 years of age
  • Immunosuppressed patients
  • Use of immunosuppressive treatments
  • Concomitant chorioretinitis of other causes
  • Pregnancy
  • Allergy to Sulfonamides
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01449877

Locations
Brazil
University of Campinas - Ophthalmology Department
Campinas, São Paulo, Brazil, 13083570
Sponsors and Collaborators
University of Campinas, Brazil
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
Principal Investigator: Rodrigo PC Lira, PhD University of Campinas
  More Information

Additional Information:
Publications:
Responsible Party: Joao Paulo Felix, MD, University of Campinas, Brazil
ClinicalTrials.gov Identifier: NCT01449877     History of Changes
Other Study ID Numbers: 356591 
Study First Received: October 6, 2011
Last Updated: July 10, 2016
Health Authority: Brazil: Ethics Committee
Brazil: National Committee of Ethics in Research
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University of Campinas, Brazil:
Ocular Toxoplasmosis
Retinochoroiditis
Prophylaxis

Additional relevant MeSH terms:
Recurrence
Toxoplasmosis
Toxoplasmosis, Ocular
Disease Attributes
Pathologic Processes
Coccidiosis
Protozoan Infections
Parasitic Diseases
Eye Infections, Parasitic
Eye Infections
Eye Diseases
Trimethoprim
Trimethoprim, Sulfamethoxazole Drug Combination
Sulfamethoxazole
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2C8 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 24, 2016