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Grand Rounds

ALTAR RCT Results: Methenamine Hippurate Prophylaxis for Recurrent UTI 

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BACKGROUND AND PURPOSE: 

  • 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 

METHODS: 

  • 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 

RESULTS: 

  • 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

CONCLUSION: 

  • 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 

Learn More – Primary Sources: 

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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Related ObG Topics:

Uncomplicated Cystitis: When to Culture, How to Treat and Recommended Prevention Strategies
RCT Results: A New Sublingual Bacterial Treatment for Recurrent UTI
Can Drinking More Water Prevent Recurrent Urinary Tract Infections?
Nitrofurantoin or Fosfomycin to treat an uncomplicated UTI?
Do Cranberries Decrease Risk of UTIs?

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