Antibiotics for Cystic Fibrosis

(ASAP-CF Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether the oral antibiotic Cephalexin can help children with cystic fibrosis who have a specific type of bacteria, MSSA, in their lungs. Researchers aim to determine if Cephalexin improves lung function over a two-week period compared to a placebo (a harmless pill resembling the real treatment). Children diagnosed with cystic fibrosis, who are stable in their symptoms and have a history of MSSA bacteria, might be suitable for this study. Participants will assist scientists in evaluating the effectiveness of Cephalexin for this condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for cystic fibrosis.

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

Research has shown that Cephalexin is generally safe and well-tolerated. In studies with children, those who took Cephalexin experienced fewer cases of the bacteria S. aureus compared to those who did not, suggesting the antibiotic effectively reduces this bacteria's presence without major issues.

Common side effects of Cephalexin can include stomach problems and allergic reactions, though these are not very common. Cephalexin has been used for a long time and remains generally safe when taken as directed. In individuals with cystic fibrosis, the drug is absorbed well, indicating efficient uptake by the body.

Overall, Cephalexin appears to be a safe treatment option, particularly for specific bacterial infections. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cystic fibrosis?

Researchers are excited about Cephalexin for cystic fibrosis because it offers a potentially simpler oral antibiotic option compared to the more complex inhaled or intravenous antibiotics typically used. Cephalexin is administered orally in either capsule or suspension format, making it more convenient for patients. While most antibiotics for cystic fibrosis patients target Pseudomonas aeruginosa, Cephalexin targets gram-positive bacteria, which could address different bacterial infections. This unique approach could lead to broader, more effective treatment options for managing infections in cystic fibrosis patients.

What evidence suggests that Cephalexin might be an effective treatment for cystic fibrosis?

Research has shown that Cephalexin, which participants in this trial may receive, effectively treats infections in people with cystic fibrosis. In one study, 16 out of 17 patients gained weight after using Cephalexin. Lung function tests, which assess lung performance, remained stable or improved in 10 out of 14 patients. Another study found that Cephalexin altered the bacteria in the body and influenced health progress in some cystic fibrosis patients, indicating possible benefits. Cephalexin is usually well absorbed by both children and adults, making it a dependable treatment option. Overall, these findings suggest that Cephalexin may help manage cystic fibrosis symptoms. ^{1 5 6 7 8}

Who Is on the Research Team?

Jonathan Rayment, MDCM

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10526061/

A Systematic Review on the Clinical Pharmacokinetics of ... Cephalexin is recommended to treat various ailments such as lower and upper respiratory tract infections, gonorrhea, urinary tract infections ( ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0022347679807854

A placebo-controlled trial of cephalexin therapy in the ... Improved weight gain in 16 of 17 patients was associated with periods of cephalexin therapy. Pulmonary function tests remained stable or improved in 10 of 14 ...

3. karger.com karger.com/dpd/article/7/4/221/108560/Cephalexin-Pharmacokinetics-in-Patients-with

Cephalexin Pharmacokinetics in Patients with Cystic Fibrosis Cephalexin was well absorbed based on a mean 24-hour urinary recovery of 89 and 93% in pediatric and adult patients. A trend for higher renal ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11953726/

Antibiotic Prophylaxis in Infants and Young Children With ... Conclusions: Although long-term prophylaxis with cephalexin successfully delayed the acquisition of S aureus, it enhanced colonization with P aeruginosa and did ...

5. nature.com nature.com/articles/pr19781018

790 CEPHALEXIN IN CYSTIC FIBROSIS: A PLACEBO- ... Cephalexin, when compared to placebo, altered the microbial flora and clinical course of some patients with cystic fibrosis.

6. cff.org cff.org/managing-cf/antibiotics

Antibiotics They should not be used to treat infections caused by viruses (such as the flu) or types of fungi, which include yeasts and molds. 16 min read.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3784810/

Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis Antibiotics and anti-inflammatory drugs are beneficial, but the most effective regimes must be determined.

8. cysticfibrosis.org.uk cysticfibrosis.org.uk/sites/default/files/2020-11/Anitbiotic%20Treatment.pdf

Antibiotic Treatment for cystic fibrosis Side-effects. Gastro-intestinal effects, hypersensitivity reactions. Notes. Not available in the UK, may be imported on a named patient basis. Can interfere.