ToxoplasmosisPhase 4NCT00004317
Pyrimethamine, Sulfadiazine, and Leucovorin in Treating Patients With Congenital Toxoplasmosis
A Phase 4 study testing Leucovorin calcium, Pyrimethamine and Spiramycin in people with Toxoplasmosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
RATIONALE: Congenital toxoplasmosis is an infection caused by the parasitic organism Toxoplasma gondii, and it may be passed from an infected mother to her unborn child. The mother may have mild symptoms or no symptoms; the fetus, however, may experience damage to the eyes, nervous system, skin, and ears. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Toxoplasmosis
- What is being tested?
- Leucovorin calcium, Pyrimethamine and Spiramycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2000to Dec 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
PROTOCOL ENTRY CRITERIA:
- Infants with congenital toxoplasmosis Toxoplasma gondii confirmed prior to age 2.5 months
- Pregnant women with evidence of toxoplasma infection by clinical observation and amniotic fluid sampling
- Acute infection acquired during gestation with evidence of fetal infection
- Untreated older children entered as controls
- Asymptomatic congenital toxoplasmosis
- Age more than 1 year
- No treatment within the first year of life
- No more than 1 month of prior therapy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Chicago
Chicago, Illinois, 60637
Rima McLeod, 773-834-4152
About this study
Official title: Phase IV Randomized Study of Pyrimethamine, Sulfadiazine, and Leucovorin Calcium for Congenital Toxoplasmosis
RATIONALE: Congenital toxoplasmosis is an infection caused by the parasitic organism Toxoplasma gondii, and it may be passed from an infected mother to her unborn child. The mother may have mild symptoms or no symptoms; the fetus, however, may experience damage to the eyes, nervous system, skin, and ears. The newborn may have a low birth weight, enlarged liver and spleen, jaundice, anemia, petechiae, and eye damage. Giving the antiparasitic drugs pyrimethamine and sulfadiazine is standard treatment for congenital toxoplasmosis, but it is not yet known which regimen of pyrimethamine is most effective for the disease.
PURPOSE: Randomized phase IV trial to determine which regimen of pyrimethamine is most effective when combined with sulfadiazine and leucovorin in treating patients who have congenital toxoplasmosis.
Read the detailed description
PROTOCOL OUTLINE: Infants are randomly assigned to 1 of 2 treatment groups. Patients are stratified by disease severity, chorioretinitis, prenatal treatment, and certainty of diagnosis at birth.
One group of infants is treated with a loading dose of oral pyrimethamine followed by a higher dose for the first two months then a lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are also given orally for 12 months. The pyrimethamine loading dose is omitted if prior prenatal therapy was given.
Another group of infants is treated with a higher dose of oral pyrimethamine for the first 6 months and then the lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are administered concurrently.
Infected fetuses of pregnant women are nonrandomly assigned to treatment with pyrimethamine, sulfadiazine, and leucovorin calcium after the first trimester. Spiramycin is administered before the fetal diagnosis is made.
Concurrent prednisone for active retinal inflammation or elevated cerebrospinal fluid protein is allowed.
Collaborating physicians will also refer historical controls, who have not been treated in the first year of life or who received one month or less therapy, and are older than one year. Absence of treatment in the first year of life will be due to parental preference, prior inadequate follow-up by the family physicians, or lack of detection or treatment of eye disease before the age of one year in otherwise asymptomatic children. These historical, untreated patients (who enter the study when they are older than one year) will be compared with treated children in the randomized study. These historical patients will not be randomized. Any abnormality requiring treatment (e.g., active chorioretinitis) in any child (including historical patients) will be treated.
All infants are followed at birth, then at age 1, 3.5, 5, 7.5, 10, 15, and 20.
- Conditions
- Toxoplasmosis
- Being tested
- Leucovorin calcium, Pyrimethamine, Spiramycin, Sulfadiazine
- Keywords
- immunologic disorders and infectious disorders, rare disease, toxoplasmosis
- Medical subject headings
- Toxoplasmosis, Immune System Diseases, Communicable Diseases, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
See arm descriptions
PyrimethamineDrug
See arm descriptions
SpiramycinDrug
Spiramycin is administered before the fetal diagnosis is made.
SulfadiazineDrug
See arm descriptions
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | This group of infants is treated with a loading dose of oral pyrimethamine followed by a higher dose for the first two months then a lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are also given orally for 12 months. The pyrimethamine loading dose is omitted if prior prenatal therapy was given. Receives: Drug: Leucovorin calcium; Drug: Pyrimethamine; Drug: Spiramycin; Drug: Sulfadiazine |
| 2 | Experimental | This group of infants is treated with a higher dose of oral pyrimethamine for the first 6 months and then the lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are administered concurrently. Receives: Drug: Leucovorin calcium; Drug: Pyrimethamine; Drug: Spiramycin; Drug: Sulfadiazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Persistent motor abnormality
Measured: At pre-specified time points
Vision
Measured: At pre-specified time points
Hearing
Measured: At pre-specified time points
New chorioretinal lesion
Measured: At pre-specified time points
IQ less than 70
Measured: At pre-specified time points
Decrease in IQ of greater than or equal to 15 points
Measured: At pre-specified time points
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 1999 (estimated)
- Study startJul 2000
- Primary completionDec 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ToxoplasmosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- University of Chicago
- Investigators
- Rima McLeod, Study chair, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004317
- Sponsor's protocol ID
- 199/11837
- Other IDs
- UCCRC-08796, MRH-850410, UCRCC-08796
- Status last verified
- May 2009
- First submitted
- 18 Oct 1999
- Last updated
- 14 May 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
McLeod R, Boyer KM, Lee D, Mui E, Wroblewski K, Karrison T, Noble AG, Withers S, Swisher CN, Heydemann PT, Sautter M, Babiarz J, Rabiah P, Meier P, Grigg ME; Toxoplasmosis Study Group. Prematurity and severity are associated with Toxoplasma gondii alleles (NCCCTS, 1981-2009). Clin Infect Dis. 2012 Jun;54(11):1595-605. doi: 10.1093/cid/cis258. Epub 2012 Apr 11.
PubMed 22499837
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV Randomized Study of Pyrimethamine, Sulfadiazine, and Leucovorin Calcium for Congenital Toxoplasmosis
- ClinicalTrials.gov ID
- NCT00004317
- Acronym / sponsor ID
- 199/11837
- Conditions
- Toxoplasmosis
- Keywords
- immunologic disorders and infectious disorders, rare disease, toxoplasmosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- University of Chicago
- Study start
- Jul 2000
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 19 Oct 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Congenital toxoplasmosis is an infection caused by the parasitic organism Toxoplasma gondii, and it may be passed from an infected mother to her unborn child. The mother may have mild symptoms or no symptoms; the fetus, however, may experience damage to the eyes, nervous system, skin, and ears. The newborn may have a low birth weight, enlarged liver and spleen, jaundice, anemia, petechiae, and eye damage. Giving the antiparasitic drugs pyrimethamine and sulfadiazine is standard treatment for congenital toxoplasmosis, but it is not yet known which regimen of pyrimethamine is most effective for the disease.
PURPOSE: Randomized phase IV trial to determine which regimen of pyrimethamine is most effective when combined with sulfadiazine and leucovorin in treating patients who have congenital toxoplasmosis.
Detailed description
PROTOCOL OUTLINE: Infants are randomly assigned to 1 of 2 treatment groups. Patients are stratified by disease severity, chorioretinitis, prenatal treatment, and certainty of diagnosis at birth.
One group of infants is treated with a loading dose of oral pyrimethamine followed by a higher dose for the first two months then a lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are also given orally for 12 months. The pyrimethamine loading dose is omitted if prior prenatal therapy was given.
Another group of infants is treated with a higher dose of oral pyrimethamine for the first 6 months and then the lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are administered concurrently.
Infected fetuses of pregnant women are nonrandomly assigned to treatment with pyrimethamine, sulfadiazine, and leucovorin calcium after the first trimester. Spiramycin is administered before the fetal diagnosis is made.
Concurrent prednisone for active retinal inflammation or elevated cerebrospinal fluid protein is allowed.
Collaborating physicians will also refer historical controls, who have not been treated in the first year of life or who received one month or less therapy, and are older than one year. Absence of treatment in the first year of life will be due to parental preference, prior inadequate follow-up by the family physicians, or lack of detection or treatment of eye disease before the age of one year in otherwise asymptomatic children. These historical, untreated patients (who enter the study when they are older than one year) will be compared with treated children in the randomized study. These historical patients will not be randomized. Any abnormality requiring treatment (e.g., active chorioretinitis) in any child (including historical patients) will be treated.
All infants are followed at birth, then at age 1, 3.5, 5, 7.5, 10, 15, and 20.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Leucovorin calcium, Drug: Pyrimethamine, Drug: Spiramycin, Drug: SulfadiazineThis group of infants is treated with a loading dose of oral pyrimethamine followed by a higher dose for the first two months then a lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are also given orally for 12 months. The pyrimethamine loading dose is omitted if prior prenatal therapy was given. |
| 2 | Experimental | Drug: Leucovorin calcium, Drug: Pyrimethamine, Drug: Spiramycin, Drug: SulfadiazineThis group of infants is treated with a higher dose of oral pyrimethamine for the first 6 months and then the lower dose for the remainder of the 12 months. Sulfadiazine and leucovorin calcium are administered concurrently. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Leucovorin calciumSee arm descriptions | Drug | 1, 2 |
| PyrimethamineSee arm descriptions | Drug | 1, 2 |
| SpiramycinSpiramycin is administered before the fetal diagnosis is made. | Drug | 1, 2 |
| SulfadiazineSee arm descriptions | Drug | 1, 2 |
Primary outcome
Persistent motor abnormality
Time frame: At pre-specified time points
Vision
Time frame: At pre-specified time points
Hearing
Time frame: At pre-specified time points
New chorioretinal lesion
Time frame: At pre-specified time points
IQ less than 70
Time frame: At pre-specified time points
Decrease in IQ of greater than or equal to 15 points
Time frame: At pre-specified time points
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2009.
- Derived from this study: PubMed 22499837McLeod R, Boyer KM, Lee D, Mui E, Wroblewski K, Karrison T, Noble AG, Withers S, Swisher CN, Heydemann PT, Sautter M, Babiarz J, Rabiah P, Meier P, Grigg ME; Toxoplasmosis Study Group. Prematurity and severity are associated with Toxoplasma gondii alleles (NCCCTS, 1981-2009). Clin Infect Dis. 2012 Jun;54(11):1595-605. doi: 10.1093/cid/cis258. Epub 2012 Apr 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rima McLeod study chair
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Leucovorin calcium, Pyrimethamine and Spiramycin in people with Toxoplasmosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 May 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Persistent motor abnormality (time frame: At pre-specified time points). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00004317, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2009.