- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02684422
Initial and Chronic Methicillin Resistant Staphylococcus Aureus (MRSA) Infection in Cystic Fibrosis (CF) (TRI-STAR)
TRI-STAR: Initial and Chronic MRSA Infection in CF (TRanslational Investigation of STaph. Aureus Resistance)
Study Overview
Status
Intervention / Treatment
Detailed Description
This is an observational, translational study examined bacterial morphology and function pre- vs. post antibiotic therapy in patients with CF who experience a pulmonary exacerbation that requires IV antibiotics.
All clinical care is dictated by the treating physician(s).
Inclusion criteria:
- Male or female with a confirmed diagnosis of CF (by sweat test and/or identification of 2 CF disease causing mutations).
- Chronic infection with MRSA defined as having had MRSA positive respiratory cultures for > 1 year with > 50% of cultures being MRSA positive.
- Being able to expectorate sputum on a consistent basis, i.e. also at the end of IV therapy 3A: starting April 2017 people with CF who cannot expectorate sputum can also participate if they will do two orapharyngeal swab cultures.
Having a pulmonary exacerbation defined for this protocol as the decision of the treating physician to start IV therapy in hospital or at home. Typically this occurs when there has been a >5% drop in FEV1 % predicted compared to the patient's baseline and increased respiratory symptoms.
- NOTE: Patients who had oral or inhaled antibiotics with or without MRSA activity but failed i.e. are changed to IV antibiotics are allowed to participate.
Exclusion criteria:
- Presence / infection with B. cepacia genomovar III (B. cenocepacia)
- Subjects who have undergone lung or liver transplant in the past (NOTE: patients listed for transplant are eligible)
- Concomitant participation and/or use of an investigational drug within 30 days of this study. Concomitant observational studies are allowed with TRI-STAR
Sputum collection:
The subject will be asked to expectorate a sputum into a sterile specimen cup solely for this study. This may be a second sample after giving one for the clinical laboratory at start of therapy. The subject will be asked for a repeat sputum sample for the study at end of therapy.
Time point definition: A) Start of therapy sample: up to 3 days prior and up to 36 hours after the first dose of anti-MRSA antibiotic. B) End of therapy: no earlier than 36 hours prior to the last dose and up to one week after completion.
Collection of clinical information: Clinical information to be collected include: Demographics, age, CF genotype, anthropometrics; FEV1 FVC, FEF 25-75 in liter and % predicted per site specific reference values; all medications (routine and those started within 2 weeks and at time of admission/IV therapy).
CF daily Symptom score: Subject will be asked to complete the CF Symptom diary for the first and last 3 days of IV therapy. For subjects admitted to the hospital this will be administered by the RC for those at home the RC will call / e-mail them as reminder or do it with them per phone.
Spirometry at conclusion of therapy: Most patients have a follow-up clinic visit or are still in the hospital at time of completion of IV therapy and spirometry is part of routine clinical assessment. NOTE: Patients who would not have a clinic visit at end of therapy may be asked to return for spirometry and sputum sample solely for this study. If the subject agrees to this, reimbursement for travel will be allowed.
Laboratory Assays:
In vitro assays done on either banked isolates in Aim 1 or sputum samples / MRSA isolates from sputum include tests on bacterial fitness as growth under different conditions; antibiotic susceptibility assays; metabolic and virulence activity and genes, and mutator rates for sputum isolates. More details are provided in the grant application.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Alabama
-
Birmingham, Alabama, United States, 35233
- University of Alabama at Birmingham
-
-
North Carolina
-
Chapel Hill, North Carolina, United States, 27599
- University of North Carolina At Chapel Hill
-
-
Washington
-
Seattle, Washington, United States, 98195
- University of Washington
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Male or female with a confirmed diagnosis of CF (clinical features and positive sweat test and/or identification of 2 CF disease causing mutations).
- At least 4 years of age or older.
- Chronic infection with MRSA defined as having had MRSA positive respiratory cultures for > 1 year with ≥ 50% of cultures being MRSA positive e.g. 2/4 of the most recent cultures grew MRSA.
- Being able to expectorate sputum on a consistent basis, i.e. also at the end of IV therapy.
- Having a pulmonary exacerbation defined for this protocol as the decision of the treating physician to start IV therapy in hospital or at home. Typically this occurs when there has been a >5% drop in FEV1 % predicted compared to the patient's baseline and increased respiratory symptoms.
NOTE: Patients who had oral or inhaled antibiotics with or without MRSA activity but failed this outpatient therapy i.e. are changed to IV anti-MRSA antibiotics are allowed to participate.(Example: was on oral doxycycline and on admission changed to ceftaroline = eligible. On oral doxycycline that is continued on admission = not eligible).
- Patient enrollment should be prioritized to those receiving IV vancomycin or ceftaroline, with secondary consideration of patients who receive oral anti-MRSA therapy (TMP-SMX or a tetracycline derivative) that was initiated on hospital admission.
- Patients on linezolid will not be included as this medication is given orally and IV and may confound analyses.
Exclusion Criteria:
- Presence / infection with B. cepacia genomovar III (=B. cenocepacia). Subjects who have undergone lung or liver transplant in the past (NOTE: patients listed for transplant are eligible)
- Concomitant participation and/or use of an investigational drug within 30 days of this study.
- Concomitant observational studies are allowed with TRI-STAR, if approved by the other study investigator or their proxy.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Cystic Fibrosis with MRSA infection
Cystic Fibrosis patients that are admitted to the hospital for IV therapy targeting MRSA will give a sputum sample and complete symptom diaries at the beginning and end of therapy. There will be no intervention administered. Inclusion criteria are ability to produce sputum and having a chronic i.e. > 2 years of positive respiratory cultures, MRSA CF lung infection. |
There are no interventions to the subjects other than collection of an expectorated sputum since this is an observational study; There are no study groups.See details per detailed study description.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Changes in presence of hypermutable MRSA isolates post-therapy compared to pre-therapy.
Time Frame: 2-3 weeks (course of IV antibiotics as determined by clinician)
|
2-3 weeks (course of IV antibiotics as determined by clinician)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Other MRSA characteristics in sputum
Time Frame: 2 weeks (course of IV antibiotics)
|
In vitro measures of MRSA fitness, antimicrobial susceptibilities, biofilm formation and exploratory in vitro bacterial assays.
|
2 weeks (course of IV antibiotics)
|
Clinical improvement with therapy
Time Frame: 2-3 weeks (course of IV antibiotics)
|
These measures for clinical improvement will be lung function and CF specific quality of life questionnaires.
|
2-3 weeks (course of IV antibiotics)
|
Collaborators and Investigators
Investigators
- Principal Investigator: Marianne S Muhlebach, MD, University of NC Chapel Hill, Dept Pediatrics
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Infections
- Respiratory Tract Diseases
- Lung Diseases
- Infant, Newborn, Diseases
- Genetic Diseases, Inborn
- Bacterial Infections
- Bacterial Infections and Mycoses
- Gram-Positive Bacterial Infections
- Pancreatic Diseases
- Fibrosis
- Cystic Fibrosis
- Staphylococcal Infections
Other Study ID Numbers
- 15-0636
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cystic Fibrosis
-
Hospital de Clinicas de Porto AlegreUnknownCystic Fibrosis | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in Children | Cystic Fibrosis With ExacerbationBrazil
-
University of Colorado, DenverCystic Fibrosis FoundationTerminatedCystic Fibrosis-related Diabetes | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in ChildrenUnited States
-
Royal College of Surgeons, IrelandThe Hospital for Sick Children; Imperial College London; Erasmus Medical Center; University College Dublin and other collaboratorsActive, not recruitingCystic Fibrosis | Adherence, Medication | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in Children | Cystic Fibrosis Liver DiseaseUnited Kingdom, Ireland
-
Herlev and Gentofte HospitalCopenhagen University Hospital, DenmarkActive, not recruitingMyocardial Infarction | Heart Diseases | Heart Failure | Stroke | Cystic Fibrosis | Heart Failure, Diastolic | Heart Failure, Systolic | Left Ventricular Dysfunction | Cystic Fibrosis-related Diabetes | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of Pancreas | Cystic Fibrosis, Pulmonary | Cystic...Denmark
-
The Hospital for Sick ChildrenCanadian Cystic Fibrosis FoundationActive, not recruitingCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in ChildrenCanada
-
Arrowhead PharmaceuticalsTerminatedCystic Fibrosis, PulmonaryAustralia, New Zealand
-
AzurRx SASCompletedCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of PancreasTurkey, Hungary
-
Dartmouth-Hitchcock Medical CenterTrustees of Dartmouth CollegeWithdrawnCystic Fibrosis-related Diabetes | Cystic Fibrosis Liver Disease | CF - Cystic FibrosisUnited States
-
University Hospital, BordeauxCompleted
-
University of PortsmouthUniversity Hospital Southampton NHS Foundation Trust; Loughborough University; Queen Alexandra HospitalTerminated
Clinical Trials on Intervention N/A. Observational study
-
Ohio State UniversityUSDA North Central - Nutrition Education Center of ExcellenceCompleted
-
George Clinical Pty LtdActelion; The George InstituteCompletedTreatment Resistant Hypertension
-
Center for Eye Research AustraliaRecruitingAge-related Macular Degeneration | Geographic Atrophy | Age Related Macular Degeneration | AMDAustralia
-
University of California, San FranciscoNational Institute of Neurological Disorders and Stroke (NINDS)Completed
-
VASCage GmbHMedical University Innsbruck; St John of God Hospital, ViennaRecruiting
-
Fondazione per la Ricerca Ospedale MaggioreCompletedBrain Injuries, Traumatic | Brain Injury Traumatic Severe | Brain Injury Traumatic ModerateItaly
-
University College DublinUniversity College CorkCompletedFood Consumption Database AnalysisIreland
-
University of North Carolina, CharlotteEunice Kennedy Shriver National Institute of Child Health and Human Development...Recruiting
-
University of Texas at AustinEnrolling by invitation
-
University of Colorado, DenverNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other collaboratorsRecruitingRheumatoid ArthritisUnited States