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

• ClinicalTrials.gov Identifier: NCT01449877
• Recruitment Status: Completed
• First Posted: October 10, 2011
• Last Update Posted: July 12, 2016
• Sponsor: University of Campinas, Brazil
• Collaborator: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Information provided by (Responsible Party): Joao Paulo Felix, University of Campinas, Brazil

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Ocular Toxoplasmosis	Drug: Trimethoprim-Sulfamethoxazole	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 141 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Influence of Trimethoprim-sulfamethoxazole for the Recurrence of Retinochoroiditis Toxoplasma Gondii
• Study Start Date: October 2011
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: November 2013

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 12 months. [ Time Frame: One year ]
2. Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 36 months. [ Time Frame: Three years ]
3. Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 48 months. [ Time Frame: Four years ]
4. Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 60 months. [ Time Frame: Five years ]
5. Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 72 months. [ Time Frame: Six years ]
6. Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 84 months. [ Time Frame: Seven years ]
7. Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 96 months. [ Time Frame: Eight years ]
8. Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 108 months. [ Time Frame: Nine years ]
9. Incidence of episodes of recurrent chorioretinitis by toxoplasmosis in the follow up of 120 months. [ Time Frame: Ten years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• 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

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:

University of Campinas 

Publications of Results:

Silveira C, Belfort R Jr, Muccioli C, Holland GN, Victora CG, Horta BL, Yu F, Nussenblatt RB. The effect of long-term intermittent trimethoprim/sulfamethoxazole treatment on recurrences of toxoplasmic retinochoroiditis. Am J Ophthalmol. 2002 Jul;134(1):41-6.

Other Publications:

Opremcak EM, Scales DK, Sharpe MR. Trimethoprim-sulfamethoxazole therapy for ocular toxoplasmosis. Ophthalmology. 1992 Jun;99(6):920-5.

Soheilian M, Sadoughi MM, Ghajarnia M, Dehghan MH, Yazdani S, Behboudi H, Anisian A, Peyman GA. Prospective randomized trial of trimethoprim/sulfamethoxazole versus pyrimethamine and sulfadiazine in the treatment of ocular toxoplasmosis. Ophthalmology. 2005 Nov;112(11):1876-82. Epub 2005 Sep 19.

Gilbert RE, See SE, Jones LV, Stanford MS. Antibiotics versus control for toxoplasma retinochoroiditis. Cochrane Database Syst Rev. 2002;(1):CD002218. Review. Update in: Cochrane Database Syst Rev. 2016;(5):CD002218.

• Responsible Party: Joao Paulo Felix, MD, University of Campinas, Brazil
• ClinicalTrials.gov Identifier: NCT01449877 History of Changes
• Other Study ID Numbers: 356591
• First Posted: October 10, 2011
• Last Update Posted: July 12, 2016
• Last Verified: July 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Joao Paulo Felix, University of Campinas, Brazil:

Ocular Toxoplasmosis; Retinochoroiditis; Prophylaxis

Additional relevant MeSH terms:

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