• Harding et al. (BMJ, 2022) compared the efficacy of methenamine hippurate for prevention of recurrent UTI with the current standard prophylaxis of daily low dose antibiotics 

• Multicenter, open label, randomized, non-inferiority trial 
  • The ALTAR trial (alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women) 
  • 8 centers across the UK  
• Participants 
  • Women ≥18 years  
  • Recurrent UTI requiring prophylactic treatment 
• Interventions 
  • Antibiotic prophylaxis for 12 months (standard treatment) | Oral once daily | Choice of antibiotic dependant on urine culture and history of allergy or intolerance 
    • Nitrofurantoin (50 or 100 mg) or 
    • Timethoprim (100 mg) or 
    • Cefalexin (250 mg)
  • Methenamine hippurate for 12 months 
    • 1 g oral twice daily  
• Study design 
  • Participants were randomly assigned 1:1 
  • Recurrent UTI definition 
    • ≥3 episodes of symptomatic UTI in the previous 12 months or 
    • ≥2 episodes in the past six months 
  • Treatment allocation was not masked and crossover between arms was allowed 
  • A patient and public involvement group predefined the non-inferiority margin as one episode of UTI per person year 
  • Intention-to-treat analyses 
    • All participants observed for at least six months 
• Primary outcome 
  • Absolute difference in incidence of symptomatic UTIs requiring antibiotic treatment 

• Standard treatment: 102 participants | Methenamine hippurate: 103 
• Incidence of UTIs requiring antibiotic treatment during the 12-month study period 
  • Standard treatment: 0.89 episodes per person year (95% CI, 0.65 to 1.12) 
  • Methenamine hippurate: 1.38 episodes per person year (95% CI, 1.05 to 1.72) 
• Methenamine hippurate was confirmed to be non-inferior to the standard treatment of low dose prophylactic antibiotics 
  • Absolute difference in UTI incidence: 0.49 (90% CI, 0.15 to 0.84) 
• Incidence of adverse reactions  
  • Standard treatment: 24% 
  • Methenamine hippurate: 28% 
  • Most reactions were mild 
  • Only 2 serious adverse reactions (severe abdominal pain and raised alanine transaminase), both in antibiotic group

• In this trial, methenamine hippurate was found to be non-inferior to antibiotic prophylaxis for the prevention of recurrent UTI 
• Methenamine hippurate may be appropriate for some women with recurrent UTI 
• Limitations of the study include lack of blinding and heterogeneity of prophylactic antibiotics prescribed 
• The authors state 

The range of a priori outcomes reported confirm clinical utility of methenamine hippurate as a non-antibiotic option for prevention of urinary tract infection in this pragmatic trial, which allows generalisability of results 

Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial 

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