Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06518291
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-12
Brief Title:
COMPARISON OF NITROFURANTOIN WITH FOSFOMYCIN in TREATING CYSTITIS IN WOMEN
Sponsor:
None
Organization:
None
Study Overview
Official Title:
COMPARISON OF NITROFURANTOIN WITH FOSFOMYCIN in TREATING CYSTITIS IN WOMEN
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Fosfomycin and nitrofurantoin are increasingly being prescribed in outpatients for the oral treatment of urinary tract infection UTI The newest guidelines for empirical treatment of women with uncomplicated urinary tract infections UTIs advise clinicians to choose among three venerable antibiotics trimethoprim-sulfamethoxazole nitrofurantoin and fosfomycin Although both nitrofurantoin and fosfomycin have shown efficacy against most urinary pathogens no recent head-to-head comparisons have been reported So this study will be conducted to compare effectiveness of both drugs
Detailed Description:
INTRODUCTION Urinary tract infection UTI is a broad term that encompasses a spectrum of infectious syndromes that affect the urinary tract anywhere from the urethra to the kidneys UTIs are one of the most common infections and it is reported that 50-60 of women have at least one UTI in their lifetime1 It is the second most common reason for antibiotic prescriptions after respiratory tract infections2 Acute uncomplicated cystitis is an infection of the bladder and urethra that affects mainly women and girls from 2 years of age and pyelonephritis is an infection of the renal parenchyma Escherichia coli is the most common causative pathogen of both diseases and accounts for approximately 85 of community-acquired UTIs and 50 of hospital-acquired UTIs345 There have been recent reports of an increasing level of antibiotic resistance in pathogens causing uncomplicated UTIs67 The 2017-2018 WHO GLASS Global Antimicrobial Resistance and Use Surveillance System report indicates 70 resistance to ceftriaxone and ciprofloxacin in E coli isolated from UTIs in Pakistan78 A previous study on UTI pathogens in Karachi found that 49 of Gram-positive and 57 of Gram-negative bacteria were resistant to ciprofloxacin59 Despite of this ciprofloxacin is readily available over the counter in an oral suspension throughout Pakistan and is prescribed widely by physicians9 This high level of resistance indicates that the use of the antibiotic as a first-line treatment for UTI in Pakistan needs to be reconsidered It has been shown in studies that there is low resistance rates to fosfomycin and nitrofurantoin1011121314 Given increasing antimicrobial resistance guidelines for the treatment of uncomplicated lower urinary tract infections UTIs were modified in 2010 to recommend nitrofurantoin and fosfomycin as first-line agents their use has since increased exponentially31215Worldwide first-line agents for uncomplicated UTIs include nitrofurantoin sulfamethoxazoletrimethoprim and fosfomycin16 Nitrofurantoin is bacteriostatic not bactericidal and must be used for 5 to 7 days It is the preferred drug for low-dose long-term prophylaxis in patients with recurrent UTIs17 Fosfomycin is FDA-approved as a 3gram single-dose therapy for uncomplicated UTIs18 A single dose will provide therapeutic urinary concentrations for 2 to 4 days and is comparable to 7- to 10-day therapy with other agents1819
OBJECTIVE As the use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection UTI This study will be conducted to compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with cystitis
RATIONALE Fosfomycin and nitrofurantoin are increasingly being prescribed in outpatients for the oral treatment of urinary tract infection UTI The newest guidelines for empirical treatment of women with uncomplicated urinary tract infections UTIs advise clinicians to choose among three venerable antibiotics trimethoprim-sulfamethoxazole nitrofurantoin and fosfomycin Although both nitrofurantoin and fosfomycin have shown efficacy against most urinary pathogens no recent head-to-head comparisons have been reported So this study will be conducted to compare effectiveness of both drugs
OPERATIONAL DEFINITIONS
1 Cystitis is infection of urinary bladder Uncomplicated cystitis refers to lower urinary tract infection in women who are otherwise healthy Complicated cystitis is associated with risk factors diabetes renal transplantation pregnancy immunocompromised indwelling catheter abnormality of urinary tract that increase the chances of antibiotic failure20
2 Pyelonephritis is infection of renal parenchyma resulting in fever pain in lumber region and vomiting
3 Adverse effects of Nitrofurantoin Headache dizziness nausea diarrhea vomiting loss of appetite chest pain numbness in hands and feet brown urine20
4 Adverse effects of Fosfomycin vaginal discharge abdominal pain headache back pain bodyaches indigestion dryness of throat heavy painful menstruation skin rash weakness20
5 Clinical response was defined as clinical resolution complete resolution of symptoms and signs of urinary tract infection without prior failure
6 Clinical failure need for additional or change in antibiotic treatment due to a urinary tract infection or discontinuation due to lack of efficacy
7 Indeterminate either persistence of symptoms without objective evidence of infection or any extenuating circumstances precluding a classification of clinical resolutionfailure
8 Microbiologic response was defined as resolution eradication of the infecting strain with no recurrence of bacteriuria 103 colony-forming unitsmL during follow-up or failure bacteriuria 103 colony- forming unitsmL with the infecting strain21
METHODOLOGY Study Design Randomized clinical trial Sampling Technique Simple random sampling Study duration six months Settings Outpatient Gynae Department Shalamar Hospital Lahore
Study will be conducted after IRB approval
Sample Size Calculation
Given
Effectiveness of Drug 1 nitrofurantoinp1 90 090 2223 Effectiveness of Drug 2 fosfomycinp2 80080 2223 Significance level α005 Power 1-β 080
The sample size n for each group can be calculated using the following formula
n Z α2 Z β2 x p11- p1 p21- p2 p1- p22
where
Z α2 is the critical value from the standard normal distribution for a tow tailed test at significance level α For α005 Z α2 196
Z β is the critical value from the standard normal distribution for the desired power For a power of 080 Z β 084
Calculating the combined variance
p11- p1 090x010009 p21- p2 080x020016 p11- p1 p21- p2 009016025
Calculating the squared difference in proportions
p1- p22 090-0802 0102 001
Putting the values in the formula
n 1960842x025 001 196001196 Each group requires 196 patients making the total sample size of 392
Intervention and Procedures Participants will be randomly assigned to either oral Nitrofurantoin 100 mg 3 times a day for 5 days or a single 3-g dose of oral Fosfomycin and instructed to contact study investigators in the absence of clinical improvement They will attend follow-up visits at 7 and 14 days after completion of antibiotic therapy Urine cultures will be collected before starting antibiotic Because of fosfomycins long half-life24 antibiotic therapy will be considered completed in both groups on day 5 after randomization
Voided midstream urine specimens will be collected in sterile containers and transported within 24 hours to laboratory where specimens will be cultured according to published recommendations Cultures will be reported positive when 103 cfumL or more of at least 1 bacterium was detected20
Data Analysis
Analysis will be performed by using SPSS version 21 Baseline characteristics will be described by mean and standard deviation The clinical and bacteriologic resolution will be compared between treatment groups using the Chi square test incidence of adverse events and other outcome measures will be compared using the Fisher exact test Patients who will show documented clinical failure and were then lost to follow-up will be included in the primary outcome analysis of any failure by day 14 while those whose response status was unknown before dropout were considered missing missing values were excluded from the primary analysis P value 005 will be considered significant
OBJECTIVE As the use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection UTI This study will be conducted to compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with cystitis
RATIONALE Fosfomycin and nitrofurantoin are increasingly being prescribed in outpatients for the oral treatment of urinary tract infection UTI The newest guidelines for empirical treatment of women with uncomplicated urinary tract infections UTIs advise clinicians to choose among three venerable antibiotics trimethoprim-sulfamethoxazole nitrofurantoin and fosfomycin Although both nitrofurantoin and fosfomycin have shown efficacy against most urinary pathogens no recent head-to-head comparisons have been reported So this study will be conducted to compare effectiveness of both drugs
OPERATIONAL DEFINITIONS
1 Cystitis is infection of urinary bladder Uncomplicated cystitis refers to lower urinary tract infection in women who are otherwise healthy Complicated cystitis is associated with risk factors diabetes renal transplantation pregnancy immunocompromised indwelling catheter abnormality of urinary tract that increase the chances of antibiotic failure20
2 Pyelonephritis is infection of renal parenchyma resulting in fever pain in lumber region and vomiting
3 Adverse effects of Nitrofurantoin Headache dizziness nausea diarrhea vomiting loss of appetite chest pain numbness in hands and feet brown urine20
4 Adverse effects of Fosfomycin vaginal discharge abdominal pain headache back pain bodyaches indigestion dryness of throat heavy painful menstruation skin rash weakness20
5 Clinical response was defined as clinical resolution complete resolution of symptoms and signs of urinary tract infection without prior failure
6 Clinical failure need for additional or change in antibiotic treatment due to a urinary tract infection or discontinuation due to lack of efficacy
7 Indeterminate either persistence of symptoms without objective evidence of infection or any extenuating circumstances precluding a classification of clinical resolutionfailure
8 Microbiologic response was defined as resolution eradication of the infecting strain with no recurrence of bacteriuria 103 colony-forming unitsmL during follow-up or failure bacteriuria 103 colony- forming unitsmL with the infecting strain21
METHODOLOGY Study Design Randomized clinical trial Sampling Technique Simple random sampling Study duration six months Settings Outpatient Gynae Department Shalamar Hospital Lahore
Study will be conducted after IRB approval
Sample Size Calculation
Given
Effectiveness of Drug 1 nitrofurantoinp1 90 090 2223 Effectiveness of Drug 2 fosfomycinp2 80080 2223 Significance level α005 Power 1-β 080
The sample size n for each group can be calculated using the following formula
n Z α2 Z β2 x p11- p1 p21- p2 p1- p22
where
Z α2 is the critical value from the standard normal distribution for a tow tailed test at significance level α For α005 Z α2 196
Z β is the critical value from the standard normal distribution for the desired power For a power of 080 Z β 084
Calculating the combined variance
p11- p1 090x010009 p21- p2 080x020016 p11- p1 p21- p2 009016025
Calculating the squared difference in proportions
p1- p22 090-0802 0102 001
Putting the values in the formula
n 1960842x025 001 196001196 Each group requires 196 patients making the total sample size of 392
Intervention and Procedures Participants will be randomly assigned to either oral Nitrofurantoin 100 mg 3 times a day for 5 days or a single 3-g dose of oral Fosfomycin and instructed to contact study investigators in the absence of clinical improvement They will attend follow-up visits at 7 and 14 days after completion of antibiotic therapy Urine cultures will be collected before starting antibiotic Because of fosfomycins long half-life24 antibiotic therapy will be considered completed in both groups on day 5 after randomization
Voided midstream urine specimens will be collected in sterile containers and transported within 24 hours to laboratory where specimens will be cultured according to published recommendations Cultures will be reported positive when 103 cfumL or more of at least 1 bacterium was detected20
Data Analysis
Analysis will be performed by using SPSS version 21 Baseline characteristics will be described by mean and standard deviation The clinical and bacteriologic resolution will be compared between treatment groups using the Chi square test incidence of adverse events and other outcome measures will be compared using the Fisher exact test Patients who will show documented clinical failure and were then lost to follow-up will be included in the primary outcome analysis of any failure by day 14 while those whose response status was unknown before dropout were considered missing missing values were excluded from the primary analysis P value 005 will be considered significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None