Urinary Tract InfectionsPhase 4AIDA-WP2NCT01966653
Study Comparing Nitrofurantoin to Fosfomycin for Acute Urinary Tract Infection in Women
A Phase 4 study testing nitrofurantoin and fosfomycin in people with Urinary Tract Infections and Cystitis, run by University Hospital, Geneva at 3 sites in 3 countries.
Trial summary
Developed before the establishment of a structured process for drug assessment, nitrofurantoin is now being prescribed frequently given the rise in multi-resistant gram-negative pathogens. Doubts remain regarding fosfomycin's long-term clinical effectiveness. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Urinary Tract Infections, Cystitis
- What is being tested?
- nitrofurantoin and fosfomycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Oct 2013to Aug 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female gender
- Age ≥ 18 years
- Written informed consent
- At least one of four key UTI symptoms that could be attributed to an uncomplicated UTI, and no alternative explanation (i.e. symptoms suggestive of STI or vulvo-vaginitis):
- Dysuria
- Urgency (including nocturia)
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- Frequency
- Suprapubic tenderness
- Urine dipstick test positive for either nitrites or leukocyte esterase
- Patient is at increased risk for resistant pathogens, e.g., FQ-resistant or ESBL-producing Enterobacteriacae
Who cannot join
- Male sex
- Pregnancy or planned pregnancy
- Known carriage of nitrofurantoin- or fosfomycin-resistant uropathogens(s)
- Concomitant antimicrobial therapy
- Use of any antibiotics in the past 7 days
- Known or suspected hypersensitivity or allergy to fosfomycin or nitrofurantoin
Show all 37Show fewer
- History of lung or liver reaction or peripheral neuropathy after use of nitrofurantoin or other nitrofurans in the past
- Pre-existing polyneuropathy
- G6PD deficiency
- Symptoms consistent with UTI in the preceding 4 weeks
- Active upper UTI (e.g. pyelonephritis, urosepsis: fever > 38.0, flank pain, chills)
- Symptoms/signs suggestive of vaginitis or sexually transmitted infection
- Indwelling catheter, nephrostomy, ureter stent or other foreign material
- Otherwise complicated UTI:
- A history of anatomical or functional abnormalities of the urogenital tract:
- Congenital abnormalities
- Polycystic kidney disease
- Obstruction or stricture of renal pelvis, ureter or urethra
- Kidney stones
- Cystocele
- Cystic diverticulae
- Change of anatomical proportions (e.g. after ureter implantation)
- Chronic vesico-urethral reflux
- Neurogenic bladder
- Severe chronic renal (creatinine clearance < 30 ml/min) or hepatic dysfunction
- Porphyria
- Immunosuppression:
- Untreated infection with the human immunodeficiency virus (HIV)
- Use of high-dose systemic corticosteroids or other immunosuppressive medication
- Chemotherapy
- Treatment with radiation
- Critical illness requiring intensive care
- Planned surgery within the next 6 weeks
- Inability to take oral drugs
- Participation in another prospective clinical trial
- Previous enrolment in the proposed study
- Inability to understand or to follow the study protocol
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: Randomised Clinical Trial Comparing Fosfomycin vs. Nitrofurantoin for Treatment of Uncomplicated Lower Urinary Tract Infection in Female Adults at Increased Risk of Antibiotic-resistant Bacterial Infection
Developed before the establishment of a structured process for drug assessment, nitrofurantoin is now being prescribed frequently given the rise in multi-resistant gram-negative pathogens. Doubts remain regarding fosfomycin's long-term clinical effectiveness. A randomized, controlled trial is needed to explore the clinical effectiveness and better define the side effect profiles of both nitrofurantoin and fosfomycin. This multi-center open trial will randomize 600 non-pregnant women at three international sites (200 each in Poland, Switzerland, and Israel) at increased risk for carriage of resistant uropathogens and with suspicion of uncomplicated lower urinary tract infection to receive either oral nitrofurantoin 100 mg three times daily for 5 days or a single 3g dose of oral fosfomycin. Patients will be followed for clinical and bacteriologic response at days 14 and 28 post therapy completion. The study hypothesis holds that nitrofurantoin will be superior to fosfomycin in clinical efficacy at final follow-up.
Read the detailed description
Developed before the establishment of a structured process for drug assessment, nitrofurantoin is now being prescribed frequently given the rise in multi-resistant gram-negative pathogens. Doubts remain regarding fosfomycin's long-term clinical effectiveness. A randomized, controlled trial is needed to explore the clinical effectiveness and better define the side effect profiles of both nitrofurantoin and fosfomycin. From autumn 2013 through summer 2016, this multi-center open trial will randomize 600 non-pregnant women at three international sites (200 each in Poland, Switzerland, and Israel) at increased risk for carriage of resistant uropathogens and with suspicion of uncomplicated lower urinary tract infection to receive either oral nitrofurantoin 100 mg three times daily for 5 days or a single 3g dose of oral fosfomycin. Patients will be followed for clinical and bacteriologic response at days 14 and 28 post therapy completion. The study hypothesis holds that nitrofurantoin will be superior to fosfomycin in clinical efficacy at final follow-up.
- Conditions
- Urinary Tract Infections, Cystitis
- Being tested
- nitrofurantoin, fosfomycin
- Keywords
- nitrofurantoin, fosfomycin, urinary tract infection, clinical efficacy, bacteriologic response
- Medical subject headings
- Urinary Tract Infections, Cystitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nitrofurantoinDrug
Also called Macrodantin, Furadantine
nitrofurantoin 100 mg po tid for 5 days
fosfomycinDrug
Also called Monuril
fosfomycin 3g po single dose
| Study group | Role | What they receive |
|---|---|---|
| nitrofurantoin | Active comparator | Nitrofurantoin will be given orally at a dose of 100 mg three times daily for 5 days. Receives: Drug: nitrofurantoin |
| fosfomycin | Active comparator | A single 3g dose of oral fosfomycin will be given. Receives: Drug: fosfomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with clinical cure, clinical failure, or indeterminate clinical response (see description below)
Clinical response is defined as either (1) clinical cure, which in turn is defined as complete resolution of symptoms with no recurrence of symptoms or signs of urinary tract infection; (2) clinical failure, defined as the need for additional, or change in, antibiotic treatment due to a urinary tract infection, OR discontinuation due to lack of efficacy; or (3) indeterminate response, defined as either persistence of symptoms without objective evidence of infection (absence of bacteriuria or pyuria) OR any extenuating circumstances precluding a classification or clinical cure/failure.
Measured: at 28 days post therapy completion
Secondary outcomes (1)
Number of participants with bacteriologic cure and with bacteriologic recurrence
Bacteriologic response is defined as either (1) bacteriologic cure, that is, eradication of the infecting strain with no recurrence of bacteriuria (<10x3 cfu/mL) during follow-up; or (2) bacteriologic recurrence, defined as bacteriuria >10x3 cfu/mL. However, bacteriologic recurrence without urinary tract symptoms will be designated asymptomatic bacteriuria and left untreated.
Measured: at 28 days post therapy completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionMay 2017 (estimated)
- Study completionAug 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission
- Responsible party
- Principal investigator, Stephen Harbarth, University Hospital, Geneva
- Investigators
- Stephan Harbarth, MD, MS, Principal investigator, University of Geneva, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01966653
- Sponsor's protocol ID
- 13-014
- Acronym
- AIDA-WP2
- Status last verified
- May 2017
- First submitted
- 10 Oct 2013
- Last updated
- 2 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Huttner A, Kowalczyk A, Turjeman A, Babich T, Brossier C, Eliakim-Raz N, Kosiek K, Martinez de Tejada B, Roux X, Shiber S, Theuretzbacher U, von Dach E, Yahav D, Leibovici L, Godycki-Cwirko M, Mouton JW, Harbarth S. Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial. JAMA. 2018 May 1;319(17):1781-1789. doi: 10.1001/jama.2018.3627.
PubMed 29710295
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Clinical Trial Comparing Fosfomycin vs. Nitrofurantoin for Treatment of Uncomplicated Lower Urinary Tract Infection in Female Adults at Increased Risk of Antibiotic-resistant Bacterial Infection
- ClinicalTrials.gov ID
- NCT01966653
- Acronym / sponsor ID
- AIDA-WP2 / 13-014
- Conditions
- Urinary Tract Infections, Cystitis
- Keywords
- nitrofurantoin, fosfomycin, urinary tract infection, clinical efficacy, bacteriologic response
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Collaborators
- European Commission
- Study start
- Oct 2013 (actual)
- Primary completion
- May 2017 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 21 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Developed before the establishment of a structured process for drug assessment, nitrofurantoin is now being prescribed frequently given the rise in multi-resistant gram-negative pathogens. Doubts remain regarding fosfomycin's long-term clinical effectiveness. A randomized, controlled trial is needed to explore the clinical effectiveness and better define the side effect profiles of both nitrofurantoin and fosfomycin. This multi-center open trial will randomize 600 non-pregnant women at three international sites (200 each in Poland, Switzerland, and Israel) at increased risk for carriage of resistant uropathogens and with suspicion of uncomplicated lower urinary tract infection to receive either oral nitrofurantoin 100 mg three times daily for 5 days or a single 3g dose of oral fosfomycin. Patients will be followed for clinical and bacteriologic response at days 14 and 28 post therapy completion. The study hypothesis holds that nitrofurantoin will be superior to fosfomycin in clinical efficacy at final follow-up.
Detailed description
Developed before the establishment of a structured process for drug assessment, nitrofurantoin is now being prescribed frequently given the rise in multi-resistant gram-negative pathogens. Doubts remain regarding fosfomycin's long-term clinical effectiveness. A randomized, controlled trial is needed to explore the clinical effectiveness and better define the side effect profiles of both nitrofurantoin and fosfomycin. From autumn 2013 through summer 2016, this multi-center open trial will randomize 600 non-pregnant women at three international sites (200 each in Poland, Switzerland, and Israel) at increased risk for carriage of resistant uropathogens and with suspicion of uncomplicated lower urinary tract infection to receive either oral nitrofurantoin 100 mg three times daily for 5 days or a single 3g dose of oral fosfomycin. Patients will be followed for clinical and bacteriologic response at days 14 and 28 post therapy completion. The study hypothesis holds that nitrofurantoin will be superior to fosfomycin in clinical efficacy at final follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| nitrofurantoin | Active comparator | Drug: nitrofurantoinNitrofurantoin will be given orally at a dose of 100 mg three times daily for 5 days. |
| fosfomycin | Active comparator | Drug: fosfomycinA single 3g dose of oral fosfomycin will be given. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Female gender
- Age ≥ 18 years
- Written informed consent
- At least one of four key UTI symptoms that could be attributed to an uncomplicated UTI, and no alternative explanation (i.e. symptoms suggestive of STI or vulvo-vaginitis):
- Dysuria
Key exclusion criteria (37 listed)
- Male sex
- Pregnancy or planned pregnancy
- Known carriage of nitrofurantoin- or fosfomycin-resistant uropathogens(s)
- Concomitant antimicrobial therapy
- Use of any antibiotics in the past 7 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nitrofurantoinAlso: Macrodantin, Furadantinenitrofurantoin 100 mg po tid for 5 days | Drug | nitrofurantoin |
| fosfomycinAlso: Monurilfosfomycin 3g po single dose | Drug | fosfomycin |
Primary outcome
Number of participants with clinical cure, clinical failure, or indeterminate clinical response (see description below)
Time frame: at 28 days post therapy completion
Clinical response is defined as either (1) clinical cure, which in turn is defined as complete resolution of symptoms with no recurrence of symptoms or signs of urinary tract infection; (2) clinical failure, defined as the need for additional, or change in, antibiotic treatment due to a urinary tract infection, OR discontinuation due to lack of efficacy; or (3) indeterminate response, defined as either persistence of symptoms without objective evidence of infection (absence of bacteriuria or pyuria) OR any extenuating circumstances precluding a classification or clinical cure/failure.
1 secondary outcome
Number of participants with bacteriologic cure and with bacteriologic recurrence
Time frame: at 28 days post therapy completion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2017.
- Derived from this study: PubMed 29710295Huttner A, Kowalczyk A, Turjeman A, Babich T, Brossier C, Eliakim-Raz N, Kosiek K, Martinez de Tejada B, Roux X, Shiber S, Theuretzbacher U, von Dach E, Yahav D, Leibovici L, Godycki-Cwirko M, Mouton JW, Harbarth S. Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial. JAMA. 2018 May 1;319(17):1781-1789. doi: 10.1001/jama.2018.3627.
- Related info.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephan Harbarth, MD, MS principal investigator
University of Geneva, Switzerland
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing nitrofurantoin and fosfomycin in people with Urinary Tract Infections and Cystitis, run by University Hospital, Geneva at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Israel, Poland, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with clinical cure, clinical failure, or indeterminate clinical response (see description below) (time frame: at 28 days post therapy completion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01966653, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2017.