Streamlined MRSA Treatment for Cystic Fibrosis

(STAR-TER Trial)

Recruiting at 8 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

42 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drugs used in the Streamlined MRSA Treatment for Cystic Fibrosis?

Research shows that minocycline and trimethoprim-sulfamethoxazole (TMP-SMX) are effective against methicillin-resistant Staphylococcus aureus (MRSA), which is a common infection in cystic fibrosis patients. Minocycline has been found to have significant activity against MRSA, and TMP-SMX is considered a viable treatment option for MRSA infections. ^{1 2 3 4 5}

Is the streamlined MRSA treatment for cystic fibrosis generally safe for humans?

The safety of the streamlined MRSA treatment, which includes drugs like minocycline and trimethoprim-sulfamethoxazole (TMP-SMX), has been studied in various conditions. Minocycline is noted for its effectiveness against MRSA with no resistance found in tested samples, and TMP-SMX is considered a viable treatment option with good lung tissue penetration. However, more studies are needed to fully understand their safety and effectiveness in cystic fibrosis patients. ^{1 2 3 6 7}

How does the drug Minocycline and Trimethoprim Sulfamethoxazole (TMP/SMX) differ from other treatments for cystic fibrosis with MRSA?

This drug combination is unique because it combines two antibiotics, Minocycline and TMP/SMX, which have been shown to be effective against MRSA, a common and challenging infection in cystic fibrosis patients. Unlike some newer and more expensive treatments, TMP/SMX is an older, cost-effective option with good lung tissue penetration, making it a practical choice for managing MRSA-related lung infections in cystic fibrosis. ^{1 7 8 9 10}

What is the purpose of this trial?

To evaluate the micro-biologic efficacy and safety of a streamlined treatment for early onset methicillin-resistant staphylococcus aureus (MRSA) in patients with cystic fibrosis.

Research Team

Marianne Muhlebach, MD

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Trimethoprim-sulfamethoxazole as a viable treatment option for infections caused by methicillin-resistant Staphylococcus aureus. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Susceptibility of methicillin-resistant Staphylococcus aureus to minocycline and other antimicrobials. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

[Bacteriological evaluations of combination therapies with minocycline and beta-lactams for methicillin-resistant Staphylococcus aureus. II. cefuzonam plus minocycline]. [2016]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Trimethoprim/sulfamethoxazole versus vancomycin in the treatment of healthcare/ventilator-associated MRSA pneumonia: a case-control study. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Successful decolonization of methicillin-resistant Staphylococcus aureus in paediatric patients with cystic fibrosis (CF) using a three-step protocol. [2013]

9. United States 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. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Newer antibacterial agents and their potential role in cystic fibrosis pulmonary exacerbation management. [2018]