Antibiotic Treatments for Cystic Fibrosis

(STOP PEDS RCT Trial)

Recruiting in Palo Alto (17 mi)

+32 other locations

Overseen by Margaret Rosenfeld, MD, MPH

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Washington, the Collaborative Health Studies Coordinating Center

Must be taking: ETI, Ivacaftor

Must not be taking: Systemic corticosteroids, Chronic oral antibiotics

Disqualifiers: Solid organ transplant, Mycobacterium abscessus, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The STOP PEDS RCT is a multicenter, parallel, open label randomized controlled trial evaluating the long-term (one year) and short-term safety and efficacy of two antibiotic treatment strategies for the management of outpatient pulmonary exacerbations (PEx) in the pediatric CF population.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. You cannot be on an acute course of oral or IV antibiotics or systemic corticosteroids within 14 days prior to enrollment, and you cannot be on chronic oral antibiotics other than azithromycin at enrollment.

What data supports the effectiveness of the drug Immediate Oral Antibiotics for treating cystic fibrosis?

A pilot study showed that a tailored therapy approach, where oral antibiotics were given only if needed, reduced antibiotic exposure in children with cystic fibrosis. This suggests that immediate oral antibiotics can be effective, but a tailored approach may help avoid unnecessary antibiotic use. ^{1 2 3 4 5}

Is it safe to use oral antibiotics for treating cystic fibrosis?

Oral antibiotics are commonly used to treat lung infections in children with cystic fibrosis, and they are generally considered safe for outpatient care. ^{2 3 5 6 7}

How is the Immediate Oral Antibiotics treatment for cystic fibrosis different from other treatments?

The Immediate Oral Antibiotics treatment for cystic fibrosis is unique because it involves starting oral antibiotics right away for pulmonary exacerbations (worsening of lung symptoms), while other treatments may delay antibiotics until symptoms worsen or use intravenous antibiotics for severe cases. This approach allows for potentially quicker management of symptoms in an outpatient setting. ^{2 3 4 5 8}

Research Team

D. B. Sanders, MD, MS

Principal Investigator

Indiana University

Margaret Rosenfeld, MD, MPH

Principal Investigator

Seattle Children's Hospital

Eligibility Criteria

This trial is for children and teens with Cystic Fibrosis who can give consent, use text messaging and the internet, perform spirometry tests, and meet specific health criteria. It's not for those recently on antibiotics or steroids, with certain infections or organ transplants, or on chronic oral antibiotics.

Inclusion Criteria

Written informed consent obtained from participant or participant's legal representative and ability to comply with study requirements

Ability to receive text messages and access the internet

I can successfully complete lung function tests.

Exclusion Criteria

Positive culture for Mycobacterium abscessus in the 12 months prior to enrollment

Presence of a condition compromising safety or data quality

I have recently taken antibiotics or steroids.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either immediate antibiotics or tailored therapy for pulmonary exacerbations, with increased airway clearance.

14 days per exacerbation

Regular monitoring visits as needed

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pulmonary function and adverse events.

1 year

Periodic in-person and remote monitoring visits

Optional Substudies

Participants may enroll in optional substudies for additional monitoring and data collection, such as throat swabs and remote monitoring.

Varies by substudy

Treatment Details

Interventions

• Immediate Oral Antibiotics (Anti-biotics)
• Tailored Treatment: Oral Antibiotics only if Additional Treatment needed (Anti-biotics)

Trial Overview The STOP PEDS RCT compares two antibiotic treatments for managing pulmonary exacerbations in kids with CF: one starts oral antibiotics only if needed later; the other begins immediate oral antibiotics. The study observes long-term (one year) and short-term safety and effectiveness.

Participant Groups

Group I: Tailored Therapy Experimental Treatment 1 Intervention

Increased airway clearance alone, with addition of oral antibiotics for worsening symptoms or failure to improve

Group II: Immediate Antibiotics Experimental Treatment 1 Intervention

Increased airway clearance plus early initiation of oral antibiotics

Immediate Oral Antibiotics is already approved in Canada for the following indications:

Approved in Canada as Immediate Oral Antibiotics for:

• Pulmonary exacerbations in pediatric cystic fibrosis patients

Who Is Running the Clinical Trial?

University of Washington, the Collaborative Health Studies Coordinating Center

Lead Sponsor

Trials

7

Recruited

10,100+

Cystic Fibrosis Foundation

Collaborator

Trials

199

Recruited

37,800+

Michael P. Boyle

Cystic Fibrosis Foundation

Chief Executive Officer since 2019

MD from Johns Hopkins University

Albert Faro

Cystic Fibrosis Foundation

Chief Medical Officer since 2023

MD

Findings from Research

In a study of 28 children with cystic fibrosis, oral antibiotic treatment for pulmonary exacerbations led to significant improvements in exacerbation scores and quality of life, as measured by the CF Questionnaire-Revised.

After two weeks of treatment, lung function improved with a median increase of 9% in forced expiratory volume (FEV1), and 81% of participants returned to at least 90% of their baseline lung function, indicating the efficacy of oral antibiotics in managing exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of oral antibiotic treated pulmonary exacerbations in children with cystic fibrosis. Hoppe, JE., Wagner, BD., Accurso, FJ., et al.[2020]

Pediatric care sites with better pulmonary function (highest quartile) were more likely to prescribe antibiotics for pulmonary exacerbations (PEx) in cystic fibrosis patients, with a significant increase in treatment odds compared to lower quartile sites.

The study found that the likelihood of receiving antibiotic treatment increased with the severity of PEx symptoms, suggesting that timely antibiotic intervention may contribute to better pulmonary function outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic treatment of signs and symptoms of pulmonary exacerbations: a comparison by care site. Schechter, MS., Regelmann, WE., Sawicki, GS., et al.[2018]

In a study of 570 cystic fibrosis patients, over half of the mild pulmonary exacerbations treated with oral antibiotics showed that lung function was already at 90% or higher of baseline FEV1 at the start of treatment, and 82% maintained this level by the end.

However, experiencing one or more mild pulmonary exacerbations in the past year was linked to a decline in lung function (FEV1), with patients having six or more exacerbations showing the steepest decline over time, indicating a negative long-term impact on lung health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of pulmonary exacerbations treated with oral antibiotics on clinical outcomes in cystic fibrosis. Stanojevic, S., McDonald, A., Waters, V., et al.[2018]

The review included five trials with 183 participants and found very low-certainty evidence regarding the effectiveness of inhaled antibiotics for treating pulmonary exacerbations in cystic fibrosis, indicating that the current studies are not strong enough to draw definitive conclusions.

Inhaled antibiotics did not show significant improvements in quality of life, lung function, or time to next exacerbation compared to intravenous antibiotics, suggesting that more robust research is needed to evaluate their potential as an alternative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. Smith, S., Rowbotham, NJ., Charbek, E.[2023]

A systematic review of four trials involving 167 participants found insufficient high-quality evidence to determine the effectiveness of inhaled antibiotics compared to intravenous antibiotics for treating pulmonary exacerbations in cystic fibrosis.

No significant differences were observed in quality of life, lung function, or the need for additional antibiotics between inhaled and intravenous treatments, indicating a need for further research to clarify the role of inhaled antibiotics in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. Smith, S., Rowbotham, NJ., Charbek, E.[2022]

References

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

A Pilot Randomized Clinical Trial of Pediatric Cystic Fibrosis Pulmonary Exacerbations Treatment Strategies. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of oral antibiotic treated pulmonary exacerbations in children with cystic fibrosis. [2020]

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

Oral antibiotic prescribing patterns for treatment of pulmonary exacerbations in two large pediatric CF centers. [2021]

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

Antibiotic treatment of signs and symptoms of pulmonary exacerbations: a comparison by care site. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Effect of pulmonary exacerbations treated with oral antibiotics on clinical outcomes in cystic fibrosis. [2018]

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

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. [2023]

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

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. [2022]

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

Treatment of pulmonary exacerbations in cystic fibrosis. [2022]