Streamlined MRSA Treatment for Cystic Fibrosis

(STAR-TER Trial)

Not currently recruiting at 9 trial locations

Overseen By Fiona Cunningham, BS

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Antibiotics, Investigational agents

Disqualifiers: Pregnancy, Abnormal renal, liver function, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 19

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with cystic fibrosis who have early MRSA infections. The study evaluates the effectiveness and safety of using a combination of oral and topical antibiotics, such as Minocycline and Trimethoprim Sulfamethoxazole (TMP/SMX), along with an oral rinse and special cleaning techniques. Suitable candidates have cystic fibrosis and have recently been diagnosed with MRSA or have experienced it a few times in recent years. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cystic fibrosis care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken antibiotics that work against MRSA or any investigational drugs within 28 days before the trial starts.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Trimethoprim Sulfamethoxazole (TMP/SMX) often treats infections like urinary tract infections and bronchitis. Although usually well-tolerated, limited information exists on its safety for repeated use in very young children. For pregnant individuals, this medication may cause birth defects and should be used with caution.

Minocycline can cause side effects, including a small risk of pancreatitis (inflammation of the pancreas) in patients with cystic fibrosis. It tends to have more side effects than some similar drugs, affecting about 13.6% of those who take it.

Mupirocin, applied to the skin, has been found safe and effective for children aged 2 months to 16 years. It works against certain bacteria, including strains of S. aureus, common in infections like MRSA.

Chlorhexidine gluconate, used for cleaning skin, can cause skin irritation and serious eye damage if not used carefully. It can also cause ear problems if it enters the middle ear.

Overall, the treatments under study have been used before, but each has its own safety considerations. Participants should consult medical professionals to determine if these treatments are suitable for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the streamlined MRSA treatment for cystic fibrosis because it combines oral, topical, and environmental approaches to tackle the infection more comprehensively. Unlike standard treatments that often focus solely on one form of antibiotic, this treatment uses Trimethoprim Sulfamethoxazole (TMP/SMX) as the primary oral antibiotic, with minocycline as an alternative for those with allergies. Additionally, it incorporates nasal Mupirocin and an oral rinse with chlorhexidine gluconate to target bacteria in multiple areas. This multi-pronged strategy, along with environmental decontamination techniques, aims to reduce MRSA colonization more effectively than traditional methods.

What evidence suggests that this trial's treatments could be effective for cystic fibrosis?

In this trial, participants will receive a combination of treatments targeting MRSA in cystic fibrosis patients. Research has shown that the antibiotic trimethoprim sulfamethoxazole (TMP/SMX), the primary oral antibiotic in this trial, is commonly used to treat bacterial infections. However, people with cystic fibrosis may require different doses because their bodies process the drug differently. For those with allergies or intolerance to TMP/SMX, minocycline serves as an alternative and has helped patients with severe cystic fibrosis gain weight and improve other health symptoms. Mupirocin, applied topically, has effectively eliminated MRSA bacteria, with some studies showing up to 86% success. Chlorhexidine gluconate, used as a mouth rinse, has reduced bacteria like MRSA, helping to prevent infections in healthcare settings. Together, these treatments in the trial aim to manage infections in cystic fibrosis patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Marianne Muhlebach, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

The STAR-TER trial is for cystic fibrosis patients aged 2 to 45 who have early MRSA colonization and are in stable health. They must be able to follow the study plan, not have severe lung function impairment, normal kidney and liver functions, and no recent MRSA-targeting antibiotic use. Women of childbearing age must agree to use barrier contraception.

Inclusion 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

You have a certain type of bacteria called MRSA in your body.

You are between 2 and 45 years old.

Exclusion Criteria

Your lung function test shows that you are breathing at less than 25% of what is expected for someone your age.

You have a type of bacteria called MRSA that is resistant to a specific antibiotic called TMP/SMX.

If you have had kidney problems in the past, your recent lab tests should show that your kidneys are working normally.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive oral trimethoprim-sulfamethoxazole or minocycline for 14 days, nasal mupirocin for 5 days, and oral disinfectant gurgle for 14 days

2 weeks

In-person visits for treatment administration

Wash-out

Participants undergo a 14-day wash-out period with no TMP-SMX or minocycline

2 weeks

Treatment Phase 2

Participants repeat the treatment protocol from Day 29 to Day 42

2 weeks

In-person visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with repeat cultures done at Day 56 ± 7 days

4 weeks

Remote visits due to COVID-19 restrictions, cultures collected at home

Long-term Follow-up

A subsequent visit will be 3 months later with their routine clinic appointment to obtain repeat cultures and clinical data

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Chlorhexidine Gluconate
• Environmental Decontamination
• Minocycline
• Mupirocin
• Trimethoprim Sulfamethoxazole (TMP/SMX)

Trial Overview

This trial tests a treatment regimen for early methicillin-resistant staphylococcus aureus (MRSA) in cystic fibrosis patients using antibiotics like TMP/SMX or Minocycline, topical Mupirocin, environmental decontamination methods, and Chlorhexidine Gluconate washes.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 5 Interventions

Subjects are treated with one oral antibiotic, one topical antibiotic, an oral rinse, and instructed to use environmental decontamination techniques. Trimethoprim Sulfamethoxazole (TMP/SMX) is the primary oral antibiotic to be used. Subjects with allergy or intolerance to TMP\_SMX will use minocycline as an alternative antibiotic. Topical antibiotics are nasal Mupirocin, and the oral rinse/gurgle with 0.12% chlorhexidine gluconate.

Minocycline is already approved in United States, European Union, Japan, India for the following indications:

Approved in United States as Minocin for:

• Acne
• Bacterial infections
• Periodontal disease
• Rosacea

Approved in European Union as Minostad for:

• Acne

Approved in Japan as Minopen for:

• Bacterial infections

Approved in India as Minoz for:

• Bacterial infections

Approved in United States as Amzeeq for:

• Acne

Approved in United States as Zilxi for:

• Rosacea

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Cook Children's Medical Center

Collaborator

Trials

8

Recruited

1,900+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

St. Louis Children's Hospital

Collaborator

Trials

30

Recruited

83,200+

Indiana University

Collaborator

Trials

1,063

Recruited

1,182,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

The combination of cefuzonam (CZON) and minocycline (MINO) shows antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with effectiveness dependent on MINO's action, particularly in MINO-susceptible strains.

While CZON + MINO was slightly less effective than the combination of cefotiam (CTM) + MINO, it demonstrated comparable antibacterial efficacy over time and is considered beneficial for treating mixed infections involving MRSA and Gram-negative bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bacteriological evaluations of combination therapies with minocycline and beta-lactams for methicillin-resistant Staphylococcus aureus. II. cefuzonam plus minocycline]. Deguchi, K., Yokota, N., Koguchi, M., et al.[2016]

Minocycline has shown significant in vitro effectiveness against both MRSA and Acinetobacter baumannii, making it a promising option for treating these serious infections.

The recent reintroduction of intravenous minocycline in the US could enhance its use in critically ill patients, and its favorable pharmacokinetic properties suggest it should be further evaluated in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minocycline--an old drug for a new century: emphasis on methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii. Bishburg, E., Bishburg, K.[2013]

Anti-MRSA antibiotics, including ceftaroline, clindamycin, and fluoroquinolone derivatives, show promise in treating acute pulmonary exacerbations in cystic fibrosis patients, but further studies are needed to confirm their pharmacokinetic and pharmacodynamic properties specifically in this population.

Some cystic fibrosis care centers are using higher doses of these antibiotics than what is FDA-approved, highlighting the need for more research on the efficacy and tolerability of various anti-MRSA treatments in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

State of the art in cystic fibrosis pharmacology-Optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: I. Anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics. Epps, QJ., Epps, KL., Young, DC., et al.[2023]

In a study of 17 pediatric cystic fibrosis patients, a three-step decolonization protocol for MRSA achieved a 47% success rate after the first five-day treatment with oral rifampicin and fusidic acid.

The overall decolonization rate increased to 94% after additional treatments, demonstrating that this protocol is effective for a significant majority of pediatric patients with MRSA in cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful decolonization of methicillin-resistant Staphylococcus aureus in paediatric patients with cystic fibrosis (CF) using a three-step protocol. Macfarlane, M., Leavy, A., McCaughan, J., et al.[2013]

In a study of 328 patients with MRSA infections, those treated with trimethoprim/sulfamethoxazole (TMP/SMX) showed better in-hospital and 90-day mortality outcomes compared to those treated with daptomycin or linezolid, although this association was not significant in multivariate analysis.

Using TMP/SMX not only proved effective but also resulted in significant cost savings, averaging $2067.40 per patient compared to the more expensive alternatives, making it a viable option for treating MRSA infections with a vancomycin MIC of 2 μg/mL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of methicillin-resistant Staphylococcus aureus infections with a minimal inhibitory concentration of 2 μg/mL to vancomycin: old (trimethoprim/sulfamethoxazole) versus new (daptomycin or linezolid) agents. Campbell, ML., Marchaim, D., Pogue, JM., et al.[2015]

In a study of 81 hospitalized patients with MRSA pneumonia, trimethoprim/sulfamethoxazole was associated with significantly lower 30-day mortality and clinical failure rates compared to vancomycin, suggesting it may be a more effective treatment option.

Both treatments had comparable rates of side effects, indicating that trimethoprim/sulfamethoxazole is not only more effective but also similarly safe as vancomycin for treating MRSA pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trimethoprim/sulfamethoxazole versus vancomycin in the treatment of healthcare/ventilator-associated MRSA pneumonia: a case-control study. Eliakim-Raz, N., Hellerman, M., Yahav, D., et al.[2018]

Pulmonary exacerbations in cystic fibrosis (CF) are common and significantly contribute to the disease's morbidity and mortality, necessitating effective antibacterial therapies tailored to individual patient and pathogen factors.

There is an increasing need for new antibiotics to manage these exacerbations, particularly against resistant pathogens like MRSA and drug-resistant Pseudomonas aeruginosa, with newer agents such as tigecycline, doripenem, and ceftobiprole showing potential but requiring further CF-specific pharmacokinetic and pharmacodynamic studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newer antibacterial agents and their potential role in cystic fibrosis pulmonary exacerbation management. Parkins, MD., Elborn, JS.[2018]

The review evaluated 4 randomized controlled trials comparing trimethoprim-sulfamethoxazole (TMP-SMX) to other antibiotics for treating community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in children, but found the evidence inconclusive for recommending TMP-SMX as a first-line treatment.

The studies primarily focused on soft tissue infections, and significant variability among the studies prevented a meta-analysis, highlighting the need for more rigorous research to clarify the effectiveness of TMP-SMX in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Trimethoprim-Sulfamethoxazole a Valid Alternative in the Management of Infections in Children in the Era of Community-Acquired Methicillin-Resistant Staphylococcus aureus? A Comprehensive Systematic Review. Rosanova, MT., Cuellar Pompa, L., Perez, G., et al.[2021]

In a study of 102 clinical isolates of MRSA, minocycline was found to be effective against all strains tested, with minimum inhibitory concentrations below 1-2 micrograms/ml, indicating its potential as a reliable treatment option.

Compared to vancomycin, which is the current standard treatment but has serious side effects and is expensive, minocycline offers a promising alternative for patients, especially those intolerant to vancomycin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Susceptibility of methicillin-resistant Staphylococcus aureus to minocycline and other antimicrobials. Qadri, SM., Halim, M., Ueno, Y., et al.[2018]

Trimethoprim-sulfamethoxazole (TMP-SMX) shows potential effectiveness against methicillin-resistant Staphylococcus aureus (MRSA) infections, but the evidence is primarily anecdotal with only one randomized clinical trial available.

Resistance rates to TMP-SMX in MRSA are variable and particularly high in certain populations, such as those with HIV, indicating that while TMP-SMX may be useful, its efficacy can be limited by resistance issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trimethoprim-sulfamethoxazole as a viable treatment option for infections caused by methicillin-resistant Staphylococcus aureus. Grim, SA., Rapp, RP., Martin, CA., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12392026/

Effects of Extended Storage of Chlorhexidine Gluconate ...

Based on their levels of antimicrobial effectiveness, CHX and BZK are classified as low-level antiseptics able to inactivate vegetative bacteria, some fungi, ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01349192?term=AREA%5BBasicSearch%5D(Effective%20Antibiotic%20Treatment%20of%20MRSA)&rank=4

Early Methicillin-resistant Staphylococcus Aureus (MRSA) ...

0.12% chlorhexidine gluconate oral rinse twice ... Microbiological efficacy of early MRSA treatment in cystic fibrosis in a randomised controlled trial.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5489741/

Microbiologic Efficacy of early MRSA treatment in cystic ...

In subjects with cystic fibrosis (CF) the prevalence of MRSA positive respiratory cultures increased from 11.9% in 2003 to 25.6% in 2013 in US CF-centers and ...

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0195670119303603

Chlorhexidine-based decolonization to reduce healthcare ...

Body surface decolonization with chlorhexidine bathing and nasal mupirocin has become a simple solution for prevention of healthcare-associated infections.

5.

trialsjournal.biomedcentral.com

trialsjournal.biomedcentral.com/articles/10.1186/1745-6215-15-223

Eradication strategy for persistent methicillin-resistant ...

Efficacy assessments will be based on change in culture results, lung function, sputum MRSA density, cystic fibrosis quality of life ...

6.

dhpsupply.com

dhpsupply.com/msds/350-580128.pdf

Hibiclens

SAFETY DATA SHEET according to OSHA Hazard Communication Standard (29 CFR 1910.1200). Hibiclens. Version number: 1b. Issued: 2019-17-06. 1(10). Product ...

7.

oleanmedicalgroup.com

oleanmedicalgroup.com/wp-content/uploads/HIBICLENS-Material-Safety-Data-Sheet.pdf

HIBICLENS Material Safety Data Sheet

Chlorhexidine gluconate. Isopropanol. (2-Propanol). 3. HAZARDS IDENTIFICATION. Form: Color: Odor: Clear liquid. Pink. Fragranced. CAS No. % (w/w). 018472-51-0.

8.

dailymed.nlm.nih.gov

dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4275eb53-1a7e-4a91-aac1-1085f40fac88

Label: HIBICLENS- chlorhexidine gluconate solution - DailyMed

These products may cause irritation or chemical burns. skin wound and general skin cleansing. Thoroughly rinse the area to be cleansed with water. Apply the ...

9.

medline.com

medline.com/media/catalog/Docs/MSDS/MSD_SDSD10662.pdf

Chlorhexidine Gluconate 4% Topical Solution

Signal word (GHS-US). : Danger. Hazard statements (GHS-US). : H315 - Causes skin irritation. H318 - Causes serious eye damage.

10.

uww.edu

uww.edu/riskmanagement/msds/data/hibiclens_zeneca_inc._9.7.89.pdf

material safety data sheet

Chlorhexidine gluconate has been reported to cause deafness when instilled in the middle ear through perforated ear drums,. Skin contact: *** ...