Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT.

Adult Anti-Bacterial Agents / adverse effects Antibiotic Prophylaxis Cost-Benefit Analysis Escherichia coli Female Hippurates Humans Male Methenamine / analogs & derivatives Trimethoprim Urinary Tract Infections / drug therapy

ANTI-BACTERIAL AGENTS ANTIBIOTIC PROPHYLAXIS COST-EFFECTIVENESS ANALYSIS ESCHERICHIA COLI METHENAMINE HIPPURATE RANDOMISED CONTROLLED TRIAL RECURRENT URINARY TRACT INFECTION

Journal

Health technology assessment (Winchester, England)

ISSN: 2046-4924

Titre abrégé: Health Technol Assess

Pays: England

ID NLM: 9706284

Informations de publication

Date de publication:
05 2022

Historique:

entrez: 10 5 2022

pubmed: 11 5 2022

medline: 12 5 2022

Statut: ppublish

Résumé

Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking. To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year. Eight UK NHS secondary care sites. A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial. A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted. The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction. Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation. This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics. Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics. This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Women with recurrent urine infections often require preventative treatment to reduce the frequency of infection episodes. Daily low-dose antibiotic medication is a guideline-recommended treatment option for these women. There is increasing concern globally regarding antibiotic-resistant infections, which has led researchers to look at alternative treatments. This trial was conducted to find out whether or not taking an alternative treatment that is not an antibiotic [i.e. methenamine hippurate (Hiprex

Sections du résumé

BACKGROUND

OBJECTIVE

To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex

DESIGN

Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year.

SETTING

Eight UK NHS secondary care sites.

PARTICIPANTS

A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial.

INTERVENTIONS

A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted.

MAIN OUTCOME MEASURES

The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction.

RESULTS

Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in

LIMITATIONS

This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation.

CONCLUSIONS

This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics.

RECOMMENDATIONS FOR RESEARCH

Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics.

TRIAL REGISTRATION

This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36.

FUNDING

This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in

Women with recurrent urine infections often require preventative treatment to reduce the frequency of infection episodes. Daily low-dose antibiotic medication is a guideline-recommended treatment option for these women. There is increasing concern globally regarding antibiotic-resistant infections, which has led researchers to look at alternative treatments. This trial was conducted to find out whether or not taking an alternative treatment that is not an antibiotic [i.e. methenamine hippurate (Hiprex

Autres résumés

Type: plain-language-summary (eng)

Identifiants

DOI: 10.3310/QOIZ6538 PMID: 35535708

pubmed: 35535708

doi: 10.3310/QOIZ6538

doi:

Substances chimiques

Anti-Bacterial Agents 0

Hippurates 0

Trimethoprim AN164J8Y0X

Methenamine J50OIX95QV

methenamine hippurate M329791L57

Banques de données

ISRCTN

['ISRCTN70219762']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1-172

Références

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