Cystic FibrosisPhase 4NCT02547116
Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis
A Phase 4 study testing Rifampin in people with Cystic Fibrosis and MRSA, run by Johns Hopkins University at 1 site in United States.
Trial summary
Methicillin-susceptible (MSSA) and Methicillin-resistant (MRSA) Staphylococcus aureus (SA) are two of the most important infectious pathogens in CF, with 69% of CF patients having lung infection with MSSA or MRSA in the last year. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis, MRSA
- What is being tested?
- Rifampin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2020to Dec 2021
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female ≥ 12 years of age
- Confirmed diagnosis of CF based on the following criteria:
- positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis) and/or
- a genotype with two identifiable mutations consistent with CF or abnormal NPD, and
- one or more clinical features consistent with the CF phenotype.
- Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
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- Two positive SCV-SA respiratory cultures in the last two years at least six months apart, plus a positive SCV-SA respiratory culture at Screening Visit and Run-in (Day -14) Visit.
- FEV1 >30% of predicted normal for age, gender, and height at Screening.
- Weight > 35 kg
- Females of childbearing potential must agree to practice one highly effective method of birth control, including abstinence. Note: highly effective methods of birth control are those, alone or in combination, that result in a failure rate less than 1% per year when used consistently and correctly. Female patients who utilize hormonal contraceptives as a birth control method must have used the same method for at least 3 months before study dosing. If the patient is using a hormonal form of contraception, patients will be required to also use barrier contraceptives as rifampin can affect the reliability of hormone therapy. Barrier contraceptives such as male condom or diaphragm are acceptable if used in combination with spermicides.
Who cannot join
- An acute upper or lower respiratory infection, pulmonary exacerbation, or change in routine therapy (including antibiotics) for pulmonary disease within 14 days of the screening visit.
- Use of oral or inhaled anti-MRSA drugs within two weeks of the Screening Visit.
- History of intolerance to rifampin or TMP/SMX, minocycline, and doxycycline.
- Resistance to rifampin or TMP/SMX, minocycline and doxycycline at screening.
- Abnormal renal function, defined as creatinine clearance <50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening.
- Abnormal liver function, defined as ≥3x upper limit of normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT), or known cirrhosis. at the time of Screening.
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- Serum hematology or chemistry results which in the judgment of the investigator would interfere with completion of the study.
- History of or listed for solid organ or hematological transplantation
- History of sputum culture with non-tuberculous Mycobacteria in the last 6 months.
- History of sputum culture with Burkholderia Cepacia in the last year.
- Planned continuous use of soft contact lenses while taking rifampin and no access to glasses.
- Taking voriconazole and unable to discontinue its use while enrolled in the study.
- Administration of any investigational drug or device within 28 days of screening or within 6 half-lives of the investigational drug (whichever is longer)
- Female patients of childbearing potential who are pregnant or lactating, or plan on becoming pregnant
- Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patient treatment, assessment, or adherence to the protocol.
- Patients taking certain drugs will be excluded from the study:
- Drugs, which are contraindicated when rifampin is used (in addition to voriconazole): i. Antiretrovirals: fosamprenavir, atazanavir, lopinavir, saquinavir, nelfinavir, tipranavir, darunavir, rilpivirine,telaprevir, boceprevir, elvitegravir, maraviroc ii. Drugs used to increase systemic exposure of antiretrovirals: Cobicistat iii. Anthelmintic/Antimalarial agents: praziquantel, artemether iv. Antianginal agent: ranolazine v. Psychiatric medications: lurasidone b. Other drugs, not contraindicated, but listed as having major drug to drug interactions i. Antiretrovirals: ritonavir, indinavir, efavirenz, nevirapine, etavirine
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21205
About this study
Methicillin-susceptible (MSSA) and Methicillin-resistant (MRSA) Staphylococcus aureus (SA) are two of the most important infectious pathogens in CF, with 69% of CF patients having lung infection with MSSA or MRSA in the last year. Wolter and co-workers recently demonstrated that a specific morphologic subtype of MSSA and MRSA, small-colony variant Staph aureus (SCV-SA), is associated with greater decline in lung function and worse clinical outcomes. SCV-SA is already recognized for its ability to contribute to persistent infection, likely due to SCV-SA's ability for intracellular growth, as well as its increased antibiotic resistance compared to normal-colony SA. To investigate the epidemiology and clinical significance of SCV-SA in CF, and explore the hypothesis that SCV-SA may require unique antibiotic treatment strategies to optimize clinical response, the investigators will perform the following:
- Characterize the epidemiology of SCV-SA infection in both an adult and pediatric CF population and investigate the clinical significance of SCV-SA infection in CF by comparing clinical characteristics and outcomes of CF patients with SCV-SA compared to those with to normal-colony MSSA/MRSA.
- Characterize the unique microbiologic characteristics of SCV-SA infection in CF by evaluating antibiotic susceptibility profiles and molecular characteristics of SCV-SA in a two large CF patient populations.
- Perform a 16-patient pilot study of a novel treatment for SCV-SA infection in CF, utilizing low dose rifampin in combination with standard anti-SA antibiotics.
These investigations will delineate the role of SCV-SA as a pathogen in CF and provide guidance to optimize treatment strategies of MSSA/MRSA CF lung infection.
- Conditions
- Cystic Fibrosis, MRSA
- Being tested
- Rifampin
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifampinDrug
Addition of Rifampin to standard anti-Staphylococcal treatment regimen
| Study group | Role | What they receive |
|---|---|---|
| Standard anti-staphylococcal antibiotic | No intervention | Not described |
| Standard anti-staphylococcal antibiotic + Rifampin | Experimental | Individuals with known, persistent small-colony variant MRSA, who are treated with standard anti-staphylococcal antibiotics, will be treated with their standard therapy in addition to Rifampin. Receives: Drug: Rifampin |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in small colony variant Staph. aureus colony forming units on induced sputum respiratory culture
Measured: Culture specimens obtained at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention
Secondary outcomes (2)
change in lung function, as measured by forced expiratory volume in one second (FEV1)
Measured: FEV1 measured at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention
patient reported symptoms/quality of life, as captured in the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
Measured: CFQ-R administered at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2015 (estimated)
- Study startDec 2020 (estimated)
- Primary completionDec 2021 (estimated)
- Study completionDec 2021 (estimated)
Why it stopped: Administrative delay
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark T Jennings, MD, MHS, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02547116
- Sponsor's protocol ID
- IRB00047491
- Status last verified
- Jan 2020
- First submitted
- 9 Sep 2015
- Last updated
- 14 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT02547116
- Acronym / sponsor ID
- IRB00047491
- Conditions
- Cystic Fibrosis, MRSA
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Administrative delay
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Dec 2020 (estimated)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 11 Sep 2015 (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.
Methicillin-susceptible (MSSA) and Methicillin-resistant (MRSA) Staphylococcus aureus (SA) are two of the most important infectious pathogens in CF, with 69% of CF patients having lung infection with MSSA or MRSA in the last year. Wolter and co-workers recently demonstrated that a specific morphologic subtype of MSSA and MRSA, small-colony variant Staph aureus (SCV-SA), is associated with greater decline in lung function and worse clinical outcomes. SCV-SA is already recognized for its ability to contribute to persistent infection, likely due to SCV-SA's ability for intracellular growth, as well as its increased antibiotic resistance compared to normal-colony SA. To investigate the epidemiology and clinical significance of SCV-SA in CF, and explore the hypothesis that SCV-SA may require unique antibiotic treatment strategies to optimize clinical response, the investigators will perform the following:
- Characterize the epidemiology of SCV-SA infection in both an adult and pediatric CF population and investigate the clinical significance of SCV-SA infection in CF by comparing clinical characteristics and outcomes of CF patients with SCV-SA compared to those with to normal-colony MSSA/MRSA.
- Characterize the unique microbiologic characteristics of SCV-SA infection in CF by evaluating antibiotic susceptibility profiles and molecular characteristics of SCV-SA in a two large CF patient populations.
- Perform a 16-patient pilot study of a novel treatment for SCV-SA infection in CF, utilizing low dose rifampin in combination with standard anti-SA antibiotics.
These investigations will delineate the role of SCV-SA as a pathogen in CF and provide guidance to optimize treatment strategies of MSSA/MRSA CF lung infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard anti-staphylococcal antibiotic | No intervention | – |
| Standard anti-staphylococcal antibiotic + Rifampin | Experimental | Drug: RifampinIndividuals with known, persistent small-colony variant MRSA, who are treated with standard anti-staphylococcal antibiotics, will be treated with their standard therapy in addition to Rifampin. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female ≥ 12 years of age
- Confirmed diagnosis of CF based on the following criteria:
- Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
- Two positive SCV-SA respiratory cultures in the last two years at least six months apart, plus a positive SCV-SA respiratory culture at Screening Visit and Run-in (Day -14) Visit.
- FEV1 >30% of predicted normal for age, gender, and height at Screening.
Key exclusion criteria (17 listed)
- An acute upper or lower respiratory infection, pulmonary exacerbation, or change in routine therapy (including antibiotics) for pulmonary disease within 14 days of the screening visit.
- Use of oral or inhaled anti-MRSA drugs within two weeks of the Screening Visit.
- History of intolerance to rifampin or TMP/SMX, minocycline, and doxycycline.
- Resistance to rifampin or TMP/SMX, minocycline and doxycycline at screening.
- Abnormal renal function, defined as creatinine clearance <50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening.
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 |
|---|---|---|
| RifampinAddition of Rifampin to standard anti-Staphylococcal treatment regimen | Drug | Standard anti-staphylococcal antibiotic + Rifampin |
Primary outcome
change in small colony variant Staph. aureus colony forming units on induced sputum respiratory culture
Time frame: Culture specimens obtained at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention
2 secondary outcomes
change in lung function, as measured by forced expiratory volume in one second (FEV1)
Time frame: FEV1 measured at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention
patient reported symptoms/quality of life, as captured in the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
Time frame: CFQ-R administered at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2021.
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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.
Mark T Jennings, MD, MHS principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rifampin in people with Cystic Fibrosis and MRSA, run by Johns Hopkins University at 1 site in United States.
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 17 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: withdrawn, as of the sponsor's last update on 14 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
change in small colony variant Staph. aureus colony forming units on induced sputum respiratory culture (time frame: Culture specimens obtained at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jan 2021.