More recent data has come from a ten year patient study by the Lower Urinary Tract Symptoms Clinic at the Whittington Hospital, London, published in the International Urogynecology Journal in 2018.
The study reviewed 624 women between 2004 and 2014 where Hiprex was prescribed alongside high dose, long-term antibiotics. 64 percent of the women said that their symptoms were very much better, with another 20 percent reporting that they were much better. The mean treatment time was just over one year.
In 2019 a trial of 86 adult patients was undertaken at Chicago’s NorthShore University Health System in the US comparing low dose prophylaxis Trimethoprim against Hiprex for recurrent UTI within a 12 month period. Results of the study showed that there was no difference between groups with regard to recurrent urinary tract infections, with 65% recurrence in the trimethoprim group versus 65% recurrence in the methenamine hippurate group. The authors concluded that methenamine hippurate may be an alternative for the prevention of recurrent urinary tract infections, with similar rates of recurrence and adverse effects to trimethoprim.
In December 2021 a published patient trial study at Newcastle University Hospitals in the UK recruited women from eight secondary care urology and urogynaecology centres in the UK from June 2016 and incorporated a 12 month treatment period followed by a six month follow-up period. Participants were adult women aged 18 years and over with recurrent UTI who had decided, in conjunction with their responsible clinician, that prophylaxis was appropriate, were eligible for inclusion. The study noted that recurrent UTI was defined as at least three episodes of symptomatic UTI in the previous 12 months or at least two episodes in the past six months.
Between 23 June 2016 and 20 June 2018, 240 participants were recruited and randomly assigned to antibiotic prophylaxis or methenamine hippurate. For those allocated to antibiotic prophylaxis, 66 (55%) received nitrofurantoin, 30 (25%) trimethoprim, 24 (20%) cefalexin. A total of 22 (18%) participants allocated to methenamine hippurate switched to receive antibiotic prophylaxis and seven (6%) vice versa. Patient follow-up was completed in January 2020.
The results of this trial noted that “incidence of antibiotic treated urinary tract infections during the 12 month treatment period was 0.9 episodes per person year in the antibiotics group and 1.4 in the methenamine hippurate group confirming non-inferiority”.
The authors concluded “In the ALTAR trial, we have demonstrated high levels of efficacy from methenamine hippurate in terms of UTI prevention, and have shown that this efficacy is comparable to the current guideline recommended prophylaxis (that is, around six month, low dose antibiotic treatment)”.
Swabs were taken during the trial to check for antibiotic-resistant bacteria. During the treatment period, more women in the antibiotic group tested positive for bacteria that were resistant to one or more antibiotics. But in the 6 months after treatment had finished, more women in the methenamine group tested positive for resistant bacteria. This unexpected (secondary) finding could be because women on methenamine received more short-course antibiotics after the study finished. More research is needed to determine whether methenamine reduces antibiotic resistance.
In 2023 the UK National Institute for Health and Care Research concluded in a published paper discussing the ALTAR trial that the results have led to an ongoing review by the National Institute for Health and Care Excellence (NICE) in the UK on whether methenamine can be offered to women with recurrent urinary tract infections. The researchers say that guidelines, such as European Association of Urology Urological Infections Guidelines, could be updated to include methenamine as an option for preventing recurrent infections. This study, along with the NICE review, will allow clinicians and patients to make shared decisions and consider using methenamine rather than antibiotics.