{"id":2129,"date":"2015-11-14T10:58:48","date_gmt":"2015-11-14T15:58:48","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=2129"},"modified":"2016-03-23T04:39:09","modified_gmt":"2016-03-23T08:39:09","slug":"ibuprofen-for-uuti-interesting-pilot-trial-but-more-to-come-soon","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/11\/14\/2129\/ibuprofen-for-uuti-interesting-pilot-trial-but-more-to-come-soon\/","title":{"rendered":"Ibuprofen For uUTI: Interesting Pilot Trial But More to Come Soon"},"content":{"rendered":"

\"uUTI<\/a><\/p>\n

At the recent AMDAC, the frequent mention of an unusual uUTI study caught my attention.\u00a0 In their review of placebo-controlled trials, FDA mentioned a study comparing ciprofloxacin with Ibuprofen (Motrin), an NSAID drug without any antibacterial activity[1]<\/a>.\u00a0 By the outcome of total symptom relief, there was no difference. Obviously, there was no difference regarding any of the dimensions of \u201cfunction or survive\u201d either.<\/p>\n

Does this mean that antibacterials are not needed to get over an episode of uUTI \/ acute cystitis? Should we withhold antibiotics for the milder forms of UTI, relying on Mother Nature and hoping that our immune system will be primed by giving it some work to do?<\/p>\n

Obviously, uUTI is an entity with a high self-cure rate, with figures anywhere between 25-50% being bandied about. Antibiotics are often prescribed with the assumption that bacterial eradication is somehow linked to clinical improvement, ie, faster improvement. After all, having a therapeutic which takes care of the cause of a condition, not just providing symptom relief is a unique attribute of antibiotics.<\/p>\n

If uUTI were a viral infection, we would not have a problem treating dysuria with an analgesic. The underlying reason for anti-infective use is to avoid ascending infection, pyelonephritis, recurrence, and complications like urosepsis and renal abscesses. Admittedly, these complications are rare.<\/p>\n

But complications do occur as there is a disease spectrum: the only difference between uUTI and pyelonephritis is \u00a0fever (not seen in all cases) or flank pain (also not in all cases). The clinical acumen does not sharply differentiate lower from upper tract involvement, a reason why pyelonephritis is often lumped together with cystitis under the rubric of uncomplicated UTI. And a patient diagnosed in the doctor\u2019s office with uUTI may feel reassured and not come back when upper tract symptoms develop.<\/p>\n

Let\u2019s review the design and findings of the Bleidorn study:<\/p>\n

\"Capture\"<\/a><\/p>\n

With only 55 evaluable patients, it would be surprising to find a more than a trend. Indeed, none of the findings reached a\u00a0level of statistical significance.<\/p>\n

Equal symptomatic response rates were seen in both arms: non-antibiotic ibuprofen was as good as ciprofloxacin. Bacterial eradication was more often achieved in the ciprofloxacin arm but this was a secondary endpoint.<\/p>\n

Of note, the\u00a0strongest trend observed in this pilot trial was the fact that more patients in the ibuprofen group had to come back for antibiotic therapy.\u00a0\u00a0 Arguably, this should have been posted as the major finding as no other factor had a similar delta in outcome between the 2 groups.<\/p>\n

There were some rather glaring omissions. For any UTI trial, a urine culture at entry is a sine qua non, and we should also be informed about the CFU count required for study entry. Thirteen patients were included in the PP analysis that should not be included as they did not have an entry culture positive for bacteria. With the urinary nitrite test positive in only 30%, we are wondering whether many of these women had CFU counts in the higher 103<\/sup> \u2013 105<\/sup>\/ml range.<\/p>\n

This was a pilot study and cannot \/ should not be criticized too harshly \u2013 a trial balloon to challenge the accepted wisdom of antibacterial therapy for all uUTI patients. It does not measure up with a\u00a0pivotal registration trial that enrolls a much larger numbers of patients (N= 450-750), is built around solid statistics and has a predefined analysis plan.<\/p>\n

It is good to know that a follow-up study is in the works. Enrollment finished in Aug. 2014 [2]<\/a>. Hence, we can expect\u00a0a publication shortly. This trial\u00a0has the quality markers of a more definitive study: 494 patients were enrolled to receive either ibuprofen 400 mg qd x3 days or fosfomycin 3 g single dose.<\/p>\n

Given the attention FDA gave to the pilot trial, the Agency\u00a0will be even more interested in\u00a0the outcome of this much larger effort. If nothing else, it may provide the information\u00a0needed to calculate M1 and M2 criteria for future non-inferiority trials. \u00a0It will not change medical practice quite yet.<\/p>\n

References:
\n<\/strong>[1]<\/a> Bleidorn et al. BMC Medicine 2010, 8<\/strong>:30
\n[2]<\/a> G\u00e1gyor et al. BMC Infectious Diseases 2012, 12:146<\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

At the recent AMDAC, the frequent mention of an unusual uUTI study caught my attention.\u00a0 In their review of placebo-controlled trials, FDA mentioned a study comparing ciprofloxacin with Ibuprofen (Motrin), an NSAID drug without any antibacterial activity[1].\u00a0 By the outcome of total symptom relief, there was no difference. Obviously, there Continue reading Ibuprofen For uUTI: Interesting Pilot Trial But More to Come Soon<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":2135,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[227,3,18],"tags":[1271,1433,403,898,1583,1430,1439,1431,1432,1375,1110],"class_list":["post-2129","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","category-the_viewpoint","tag-allphase-pharma-consulting","tag-antibiotic-benefit","tag-antibiotic-blog","tag-fosfomycin","tag-harald-reinhart","tag-indomethacin","tag-motrin","tag-nsaid","tag-placebo-controlled","tag-uti","tag-uuti"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/uUTI-study-slider.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-yl","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":2246,"url":"https:\/\/allphasepharma.com\/dir\/2016\/01\/21\/2246\/ibuprofen-for-uuti-part-2-antibiotic-or-nsaid-or-both-or-neither\/","url_meta":{"origin":2129,"position":0},"title":"Ibuprofen for uUTI (Part 2): Antibiotic or NSAID? Or Both? Or Neither?","author":"Harald","date":"January 21, 2016","format":false,"excerpt":"While the news is\u00a0abuzz with reports of Zika virus coming to a place near you, an interesting article on a much more mundane topic \u2013 the treatment of uncomplicated UTIs \u2013 should be\u00a0competing for your attention. It is a\u00a0publication we have been\u00a0waiting for, as mentioned in an earlier blog. Results\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"ibuprofen fosfomycin - slider copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/01\/ibuprofen-fosfomycin-slider-copy.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/01\/ibuprofen-fosfomycin-slider-copy.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/01\/ibuprofen-fosfomycin-slider-copy.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":4126,"url":"https:\/\/allphasepharma.com\/dir\/2025\/04\/03\/4126\/blujepa-gepotidacin-fda-approval-uuti-efficacious-e-coli-nitrofurantoin\/","url_meta":{"origin":2129,"position":1},"title":"BLUJEPA \/ Gepotidacin APPROVED FOR UNCOMPLICATED UTI – 1","author":"Harald","date":"April 3, 2025","format":false,"excerpt":"GSK\u2019s pipeline in anti-infectives is impressive. 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