Table of contents

• Overview of Trimethoprim trials
• Urinary tract and kidney-related infection studies
• Bloodstream and serious infection studies
• Bone, joint, and implant infection studies
• Special patient groups and prevention studies
• Main endpoints used in the trials

Overview of Trimethoprim trials

The trial data show Trimethoprim mainly as part of Sulfamethoxazole and Trimethoprim, used in studies of infection treatment, step-down therapy, and prevention.^[1] Most studies are Phase 3 trials, with some Phase 2 studies and one Phase 1 transplant study.^[2] The studies include adults, children, transplant recipients, and people with serious bacterial infections or urinary tract problems.^[3]

Several trials compare shorter treatment with longer treatment, or oral treatment with intravenous treatment.^[1] Other trials study prevention of infection after surgery, after transplant, or in people with repeated infections.^[4]

Urinary tract and kidney-related infection studies

Many Trimethoprim-related trials focus on urinary tract infection (UTI), which means infection in the urinary system.^[3] One Phase 3 trial studies children 1 month to 3 years old with acute pyelonephritis, a kidney infection, and compares 3 days of intravenous antibiotics followed by 7 days of oral antibiotics with 3 days of intravenous treatment alone.^[3] The main outcome is recurrence of febrile UTI within 28 days after treatment ends.^[3]

Another Phase 3 trial studies kidney transplant recipients with pyelonephritis and tests whether 7 days of treatment is not worse than 14 days of treatment.^[1] Its main result is clinical cure at day 30, defined as fever below 38°C and no UTI symptoms, with no extra antibiotic treatment needed.^[1] A separate Phase 3 trial studies women with recurrent urinary tract infections and compares methenamine hippurate with antibiotic prevention, including SEPTRIN, which contains Trimethoprim in the source data.^[5]

Trimethoprim also appears in studies of febrile UTI in adults and in children with posterior urethral valves, a urinary condition that can affect bladder drainage.^[6] These studies look at clinical response, time to first infection, and whether antibiotic strategies can reduce infection risk.^[6]

Bloodstream and serious infection studies

Some trials study serious infections in hospitalized patients, where Trimethoprim is used as part of a treatment option.^[7] One Phase 3 study in adults with Gram-negative bacteraemia compares early switch to oral fluoroquinolones or Trimethoprim-sulfamethoxazole with continued intravenous therapy.^[1] The main endpoint is 30-day all-cause mortality.^[1]

Another Phase 3 trial studies short-course treatment for Gram-negative bacteremia with a urinary source in hospitalized, immunocompetent adults.^[8] Its main outcome is 90-day survival without clinical or microbiological failure.^[8] In catheter-related bloodstream infection due to Staphylococcus aureus, Trimethoprim-sulfamethoxazole is one of several treatments being compared, and the main outcome is clinical cure without relapse at day 30.^[7]

Trimethoprim is also part of a Phase 3 trial in severe anti-GBM antibody disease, also called Goodpasture disease, where the main result is kidney function at 6 months measured by eGFR, which means estimated glomerular filtration rate, a test of how well the kidneys filter blood.^[2]

Bone, joint, and implant infection studies

Several trials use Trimethoprim-related regimens in bone and joint infections.^[4] One Phase 3 study in prosthetic joint infection compares treatment strategies and includes Cotrimoxazol, which contains Trimethoprim in the source data.^[9] Its main outcome is treatment success 15 months after surgery, defined by no infection-related re-surgery, no new antibiotic treatment for the same joint, no ongoing antibiotics at the end of follow-up, and no death.^[9]

Another Phase 3 trial studies infections of osteosynthesis material after long bone fractures.^[4] This trial checks whether a shorter antibiotic course works as well as a longer one after surgical treatment with implant retention or removal.^[4] The main outcome is clinical failure, including return of symptoms, need to stop or change antibiotics, and fracture healing measures.^[4]

A Phase 3 study in diabetic foot osteomyelitis also includes Cotrim forte, which contains Trimethoprim in the source data.^[10] The main outcome is healed ulcer or osteomyelitis resolution at 12 and 24 weeks, with no further antimicrobial treatment and stable wound closure.^[10]

Special patient groups and prevention studies

Trimethoprim appears in trials involving special patient groups, including children with cancer, transplant recipients, and people with immune-related conditions.^[11] One Phase 1 kidney transplant study evaluates the safety of Treg02, a cell therapy, and includes Cotrim-ratiopharm in the background treatment list.^[12] The trial measures acute toxicity, over-suppression of the immune system, chronic toxicity, and biopsy-confirmed acute rejection within 60 weeks.^[12]

A Phase 1 study in children with malignant brain tumors measures antibiotic concentrations in cerebrospinal fluid, the fluid around the brain and spinal cord.^[11] This study includes Eusaprim, which contains Trimethoprim in the source data, and measures pharmacokinetic parameters, meaning how the body absorbs and moves the drug.^[11]

Another Phase 3 study in adults undergoing allogeneic blood and marrow transplant includes Bactrim in the control regimen and measures fungal-free survival at day 90.^[11] In hematology and cancer-related studies, Trimethoprim-containing prophylaxis is also used alongside other supportive treatments to help prevent infections during intensive therapy.^[13]

Main endpoints used in the trials

The trials use several types of endpoints, or main results, depending on the condition being studied.^[3] Common endpoints include clinical cure, symptom resolution, recurrence of infection, treatment failure, mortality, and kidney function.^[1] Some trials also measure antibiotic exposure in the blood, microbiological clearance, quality of life, or safety events such as serious adverse events.^[14]

For patient safety, some studies focus on whether treatment causes serious side effects or whether immune suppression, infection, or rejection occurs in transplant patients.^[12] In other studies, the main goal is not to prove a new treatment is better, but to show that a shorter or simpler treatment is not worse than the standard approach.^[1]