Antibiotics for Cystic Fibrosis

(ASAP-CF Trial)

Recruiting at 1 trial location

Overseen By Fareeha Khan

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: University of British Columbia

Must not be taking: Chronic antibiotics, Corticosteroids

Disqualifiers: Chronic infections, Organ transplant, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

86 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial requires no changes in respiratory medications within 28 days before enrollment and no chronic daily antibiotic use.

Is cephalexin safe for humans?

Cephalexin is generally considered safe for humans, with common side effects including skin rashes, itching, and mild stomach issues. Allergic reactions occur in a small percentage of people, and serious side effects are rare. ^{1 2 3 4 5}

How does the drug Cephalexin differ from other treatments for cystic fibrosis?

Cephalexin is a type of antibiotic known as a cephalosporin, which is generally used to treat bacterial infections by stopping the growth of bacteria. While it is not specifically highlighted in the research for treating Pseudomonas infections in cystic fibrosis, it may be considered for its broad-spectrum antibacterial properties. However, other cephalosporins like ceftazidime and cefsulodin are more commonly used for cystic fibrosis due to their specific effectiveness against Pseudomonas aeruginosa, a common bacteria in these patients. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial tests if the antibiotic Cephalexin can help children with cystic fibrosis and a specific bacterial infection (MSSA) by improving their lung function. Cephalexin has been used in previous studies for antistaphylococcal prophylaxis in infants and young children with cystic fibrosis.

Research Team

Jonathan Rayment, MDCM

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for children with cystic fibrosis who have had a Staphylococcus aureus infection in the past two years, are between 3 years and under 17, weigh at least 10 kg, and haven't changed their respiratory meds recently. They can't join if they have chronic infections with certain bacteria or use daily antibiotics.

Inclusion Criteria

You have been diagnosed with cystic fibrosis (CF) through specific tests or screenings, and you meet certain age, weight, and symptom criteria.

Exclusion Criteria

The participant should not have made changes to their respiratory medications within the last 28 days, have certain chronic infections, be using certain antibiotics or steroids, or have certain medical conditions. They should also not be pregnant or have certain respiratory symptoms or diagnoses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either oral Cephalexin or placebo for 2 weeks to assess lung function improvement

2 weeks

Daily administration, 3 times a day

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cephalexin
• Placebo

Trial Overview The study tests whether Cephalexin (an oral antibiotic) improves lung function in stable cystic fibrosis patients compared to a placebo. It's randomized and double-blinded, meaning neither the researchers nor participants know who gets the real medicine during the two-week trial.

Participant Groups

Group I: Cephalexin Experimental Treatment 1 Intervention

Oral cephalexin (available in capsule or suspension format) dosed at 150 mg/kg/day. Doses will be administered 3 times a day for 2 weeks.

Group II: Placebo Placebo Group 1 Intervention

The placebo will be available in both capsule and suspension format. Doses will be administered 3 times a day for 2 weeks

Cephalexin is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in European Union as Cefalexin for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in Canada as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in Switzerland as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

The Hospital for Sick Children

Collaborator

Trials

724

Recruited

6,969,000+

Findings from Research

In two randomized studies involving 343 patients, cephalexin hydrochloride was found to be as effective as cephalexin monohydrate for treating skin and soft tissue infections, with high response rates of 95.7% and 96.5% respectively.

Both formulations demonstrated a similar safety profile, with only 4.95% of patients experiencing adverse events, indicating that cephalexin hydrochloride is a safe and effective option for these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections. Kumar, A., Murray, DL., Hanna, CB., et al.[2021]

Cephalosporins are generally well tolerated antibiotics, with allergic reactions occurring in 0.9 to 3.2% of patients, and serious adverse effects are rare, affecting less than 1% of patients.

While cephalosporins are considered safe, subtle differences in their chemical structure can lead to specific adverse effects, necessitating ongoing monitoring for potential reactions, especially with the introduction of new agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of newer cephalosporins. An update. Thompson, JW., Jacobs, RF.[2018]

In a study involving 99 patients with respiratory and urinary tract infections, cefetamet pivoxil (CAT) showed a clinical efficacy rate of 94.1%, while cefixime (CFX) had a rate of 91.7%, indicating both treatments are highly effective.

The safety profiles of CAT and CFX were similar, with adverse drug reactions occurring in 9.1% of the CAT group and 7.4% of the CFX group, suggesting that both medications are safe for use in treating bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A randomized controlled clinical study of cefetamet pivoxil versus cefixime in the treatment of 99 cases bacterial infections]. Zhao, C., Li, J., Hao, F.[2016]

Acute rhinosinusitis is a leading cause of antibiotic prescriptions globally, raising concerns about antibiotic resistance and the safety of commonly used antibiotics like macrolides and fluoroquinolones.

A surveillance study on the new cephalosporin drug Spectracef (Cefditoren) showed promising efficacy and safety for treating acute bacterial rhinosinusitis, particularly due to its different chemical structure that may reduce the risk of cross-allergy with penicillins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A study of the efficacy and safety of new cephalosporin in the treatment of acute bacterial rhinosinusitis]. Savlevich, EL., Kozlov, VS., Zharkykh, MA.[2018]

Cefixime was tested in multicenter trials involving 406 patients (137 children and 269 adults) with respiratory and urinary tract infections, showing positive clinical and bacteriological outcomes in 76-90% of cases.

The medication had a low incidence of adverse reactions, such as skin eruptions and dyspepsia, which were rare and did not necessitate specific treatment, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of cefixime (results of multicenter trials)]. Sereda, EV., Gusel', VA., Feshchenko, IuI., et al.[2016]

Ceftazidime was found to be the most effective beta-lactam antibiotic against Pseudomonas aeruginosa in cystic fibrosis patients, with a low resistance rate of only 6%, and it successfully eradicated associated infections like Staphylococcus aureus.

In a study involving 111 cystic fibrosis patients, while ceftazidime, cefsulodin, and piperacillin showed promising results, only 23% of cases achieved complete eradication of Pseudomonas, highlighting the need for careful use of these antibiotics against resistant strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative antibiotics for the treatment of Pseudomonas infections in cystic fibrosis. Mastella, G., Agostini, M., Barlocco, G., et al.[2019]

In a study involving 20 cystic fibrosis patients treated with cefsulodin for chronic Pseudomonas aeruginosa infections, 90% of the bacterial strains were sensitive to the drug, leading to significant clinical improvement in many cases, including the complete disappearance of the bacteria in 5 patients.

Cefsulodin was well tolerated with minimal side effects, making it a promising alternative to carbenicillin for patients with allergies to that medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of pulmonary Pseudomonas aeruginosa infection in cystic fibrosis with cefsulodin. Møller, NE., Koch, C., Vesterhauge, S., et al.[2019]

Third-generation cephalosporins, particularly cefsulodin and ceftazidime, are effective and safe options for treating acute pulmonary exacerbations in cystic fibrosis patients due to their intrinsic anti-Pseudomonas activity.

While these antibiotics have improved gram-negative activity over generations, they may have reduced effectiveness against gram-positive bacteria, highlighting the need for careful selection based on the specific needs of cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cephalosporin therapeutics in cystic fibrosis. Blumer, JL., Stern, RC., Yamashita, TS., et al.[2019]

In a study of 18 pediatric patients (9 with cystic fibrosis), the pharmacokinetics of ceftolozane/tazobactam were found to be similar between children with and without cystic fibrosis, indicating that dosing adjustments may not be necessary for this population.

All patients achieved the necessary pharmacokinetic/pharmacodynamic targets for effective treatment, suggesting that ceftolozane/tazobactam could be a viable option for treating pulmonary exacerbations in cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma pharmacokinetics of ceftolozane/tazobactam in pediatric patients with cystic fibrosis. Arrieta, AC., Ang, JY., Zhang, Z., et al.[2020]

A national survey of pharmacists at Cystic Fibrosis Foundation-accredited centers revealed that 78.6% of pediatric pharmacists and 96% of adult pharmacists use extended-interval tobramycin dosing, typically starting at 10 mg/kg every 24 hours, aiming for a serum concentration of 20 to 40 mg/L.

The survey highlights the need for standardized dosing and monitoring strategies for tobramycin and beta-lactams in cystic fibrosis treatment, as most pharmacists reported using these medications in combination, with a focus on optimizing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach. Zobell, JT., Epps, K., Kittell, F., et al.[2020]

References

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

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Adverse effects of newer cephalosporins. An update. [2018]

3. China pubmed.ncbi.nlm.nih.gov

[A randomized controlled clinical study of cefetamet pivoxil versus cefixime in the treatment of 99 cases bacterial infections]. [2016]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[A study of the efficacy and safety of new cephalosporin in the treatment of acute bacterial rhinosinusitis]. [2018]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of cefixime (results of multicenter trials)]. [2016]

6. England pubmed.ncbi.nlm.nih.gov

Alternative antibiotics for the treatment of Pseudomonas infections in cystic fibrosis. [2019]

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

Treatment of pulmonary Pseudomonas aeruginosa infection in cystic fibrosis with cefsulodin. [2019]

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

Cephalosporin therapeutics in cystic fibrosis. [2019]

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

Plasma pharmacokinetics of ceftolozane/tazobactam in pediatric patients with cystic fibrosis. [2020]

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

Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach. [2020]