Recurrent Urinary Tract Infections and Heparin (RUTIH Trial)
キーワード
概要
説明
Primary Objectives: The specific aims of this study are to 1) demonstrate that Heparin bladder instillations reduce the number of UTI episodes; 2) demonstrate Heparin bladder instillations increase median intervals between UTI; and 3) demonstrate that Heparin bladder instillations decrease urine inflammatory (NGAL) levels. Study Design: This study will be a randomized, double-blind, placebo-controlled trial of subjects treated for documented recurrent urinary tract infections with heparin bladder instillation versus sterile saline instillations. The study recruits women (n = 30) with 3 or more UTI episodes in one year from the patient population at The University of Oklahoma Health Sciences Center (OUHSC) and The University of Oklahoma-Tulsa (OU-Tulsa) and randomly assigns them to treatment as usual care with sterile saline instillation (n =15) or treatment as usual with heparin bladder instillations (n = 15). Subjects are given 6 weekly bladder instillations with interval follow-ups; the primary outcome measures are number of UTI episodes during the six month study period and a survival analysis assesses time to the next UTI. The usual care of this study is antibiotic treatment for UTI only. Urine samples will be collected at certain intervals. Analysis: We will seek a statistically significant difference of the recurrent UTI rate for 6 months between heparin instillation and sterile saline instillation group. Assuming Recurrent UTI rate of sterile saline bladder instillation is 2.3.3 UTI episodes per six months, a 35% reduction in the recurrent UTI rate is deemed significant based on previous literature. A sample size 30 (15 for each group) will achieve 60% power to detect a 35% reduction in recurrent UTI rate at a 0.05 significance level. Allowing for a 25% drop out, a total of 30 subjects will be required. Significance: Recurrent UTIs are challenging to manage, especially if microbiological results are equivocal. In women who suffer from frequent recurrences, daily antibiotic use is the most effective strategy for recurrent UTI prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture. However even with this traditional approach of continuous antibiotic for 6 to 12 months, the rate of UTI was only reduced during prophylaxis and the rate of UTI was unchanged after stopping antibiotic treatment. Increasing antibiotic resistance rates require immediate identification of innovative alternative prophylactic therapies. The lack of non-antibiotic therapies gives an opportunity to develop innovative strategies to decrease recurrent UTIs and decrease the burden of UTIs. This study will augment the current evidence available on the aggregate effects of a treatment that emphasizes the optimization of both antibiotic regimens and non-antibiotic interventions.
日付
| 最終確認済み: | 03/31/2020 |
| 最初に提出された: | 09/14/2014 |
| 提出された推定登録数: | 09/17/2014 |
| 最初の投稿: | 09/21/2014 |
| 最終更新が送信されました: | 04/09/2020 |
| 最終更新日: | 04/13/2020 |
| 実際の研究開始日: | 11/27/2017 |
| 一次完了予定日: | 11/30/2020 |
| 研究完了予定日: | 06/30/2021 |
状態または病気
介入/治療
Drug: Intravesical heparin
Other: Placebo
段階
アームグループ
| 腕 | 介入/治療 |
|---|---|
| Experimental: Intravesical heparin Recurrent UTI subject receives intravesical heparin once every week for 6 weeks | Drug: Intravesical heparin Heparin bladder instillation |
| Active Comparator: Placebo Recurrent UTI subject receives intravesical saline once every week for 6 weeks | Other: Placebo Intravesical saline |
適格基準
| 研究の対象となる年齢 | 18 Years に 18 Years |
| 研究に適格な性別 | Female |
| 健康なボランティアを受け入れる | はい |
| 基準 | Inclusion Criteria: - Women aged 18-85 with history of recurrent urinary tract infections. - Definition of Recurrent UTI: if experienced either more than 3 symptomatic UTI episodes in the past year (including the index infection) or 2 such episodes in the past 6 months. - Definition of UTI: >103 cfu/mL of a uropathogen in midstream urine culture from a woman experiencing more than 2 symptoms of cystitis (dysuria, urgency, frequency, suprapubic pain, or hematuria) or, in the absence of a culture, demonstration of pyuria on urinalysis and more than 2 urinary symptoms, as well as complete and rapid resolution of symptoms in response to antibiotic therapy for UTI. Exclusion Criteria: - Taking any anticoagulant such as warfarin sodium, heparin - Taking any thrombolytic agent such as a tissue plasminogen activator or streptokinase - Known aneurysm, thrombocytopenia, hemorrhagic disease, hemophilia, gastrointestinal ulceration, polyps, or diverticula - Known hypersensitivity to heparin - History of, or currently has neurogenic bladder, pelvic irradiation or chemical cystitis - Presence of urethral, pelvic, or rectal carcinoma, Benign or malignant bladder tumors - Tuberculous cystitis, urinary schistosomiasis - Bladder or ureteral calculi, urethral or bladder obstruction, augmentation cystoplasty, cystectomy, supratrigonal denervation of the bladder (cystolysis), neurectomy, or implanted peripheral nerve stimulator that has affected bladder function; Microscopic hematuria as defined as > 5 red blood cells (RBC) /high power field at baseline visit without a negative workup within the last year - Positive pregnancy test at the baseline visit, are pregnant or lactating, or are planning to become pregnant during the study period - Have history of uterine, cervical or vaginal cancer during the past 3 years - Clinically significant vaginitis at baseline visit |
結果
主な結果の測定
1. Change from Baseline in UTI rate at 6 months [6 months]
二次的な結果の測定
1. Change from Baseline in median time to UTI recurrence at 6 months [6 months]
その他の成果対策
1. Change from Baseline in NGAL levels at 6 months(NGAL) levels after Heparin treatment [6 months]
