Browsing by Author "Goss, Christopher H."

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    A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment
    (American Thoracic Society, 2021) Goss, Christopher H.; Heltshe, Sonya L.; West, Natalie E.; Skalland, Michelle; Sanders, Don B.; Jain, Raksha; Barto, Tara L.; Fogarty, Barbra; Marshall, Bruce C.; VanDevanter, Donald R.; Flume, Patrick A.; STOP2 Investigators; Pediatrics, School of Medicine
    Rationale: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. Objectives: To test differing durations of intravenous antimicrobials for CF exacerbations. Methods: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7–10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days’ total antimicrobial duration; all others were randomized to 14 or 21 days’ duration. Measurements and Main Results: The primary outcome was percent predicted FEV1 (ppFEV1) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV1 change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV1 changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. Conclusions: Among adults with CF with early treatment improvement during exacerbation, ppFEV1 after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days.
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    Health care costs in a randomized trial of antimicrobial duration among cystic fibrosis patients with pulmonary exacerbations
    (Elsevier, 2022) Gold, Laura S.; Hansen, Ryan N.; Patrick, Donald L.; Tabah, Ashley; Heltshe, Sonya L.; Flume, Patrick A.; Goss, Christopher H.; West, Natalie E.; Sanders, Don B.; VanDevanter, Donald R.; Kessler, Larry; Pediatrics, School of Medicine
    Background: The purpose of these analyses was to determine whether overall costs were reduced in cystic fibrosis (CF) patients experiencing pulmonary exacerbation (PEx) who received shorter versus longer durations of treatment. Methods: Among people with CF experiencing PEx, we calculated 30-day inpatient, outpatient, emergency room, and medication costs and summed these to derive total costs in 2020 USD. Using the Kaplan-Meier sample average (KMSA) method, we calculated adjusted costs and differences in costs within two pairs of randomized groups: early robust responders (ERR) randomized to receive treatment for 10 days (ERR-10 days) or 14 days (ERR-14 days), and non-early robust responders (NERR) randomized to receive treatment for 14 days (NERR-14 days) or 21 days (NERR-21 days). Results: Patients in the shorter treatment duration groups had shorter lengths of stay per hospitalization (mean ± standard deviation (SD) for ERR-10 days: 7.9 ± 3.0 days per hospitalization compared to 10.1 ± 4.2 days in ERR-14 days; for NERR-14 days: 8.7 ± 4.9 days per hospitalization compared to 9.6 ± 6.5 days in NERR-21 days). We found statistically significantly lower adjusted mean costs (95% confidence interval) among those who were randomized to receive shorter treatment durations (ERR-10 days: $60,800 ($59,150 - $62,430) vs $74,420 ($72,610 - $76,450) in ERR-14 days; NERR-14 days: $66,690 ($65,960-$67,400) versus $74,830 ($73,980-$75,650) in NERR-21 days). Conclusions: Tied with earlier evidence that shorter treatment duration was not associated with worse clinical outcomes, our analyses indicate that treating with shorter antimicrobial durations can reduce costs without diminishing clinical outcomes.
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    Oral Glutathione and Growth in Cystic Fibrosis: A Multicenter, Randomized, Placebo-controlled, Double-blind Trial
    (Wolters Kluwer, 2020) Bozic, Molly; Goss, Christopher H.; Tirouvanziam, Rabindra M.; Baines, Arthur; Kloster, Margaret; Antoine, Liebe; Borowitz, Drucy; Schwarzenberg, Sarah Jane; GROW study group; Pediatrics, School of Medicine
    Objectives: The nutritional status of children with cystic fibrosis (CF) is associated with mortality and morbidity. Intestinal inflammation may contribute to impaired digestion, absorption, and nutrient utilization in patients with CF and oral glutathione may reduce inflammation, promoting improved nutritional status in patients with CF. Methods: The GROW study was a prospective, multicenter, randomized, placebo-controlled, double-blind, phase II clinical trial in pancreatic insufficient patients with CF between the ages of 2 and 10 years. Patients received reduced glutathione or placebo orally daily for 24 weeks. The primary endpoint was the difference in change in weight-for-age z-scores from baseline through week 24 between treatment groups. Secondary endpoints included other anthropometrics, serum, and fecal inflammatory markers in addition to other clinical outcomes. Results: Fifty-eight participants completed the study. No significant differences were seen between glutathione (n = 30) and placebo (n = 28) groups in the 6-month change in weight-for-age z-score (-0.08; 95% CI: -0.22 to 0.06; P = 0.25); absolute change in weight (kg) (-0.18; 95% CI: -0.55 to 0.20; P = 0.35); or absolute change in BMI kg/m (-0.06; 95% CI: -0.37 to 0.25; P = 0.69). There were no significant differences in other secondary endpoints. Overall, glutathione was safe and well tolerated. Conclusions: Oral glutathione supplementation did not impact growth or change serum or fecal inflammatory markers in pancreatic insufficient children with CF when compared with placebo.
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    Rates of adverse and serious adverse events in children with cystic fibrosis
    (Elsevier, 2021) Pittman, Jessica E.; Khan, Umer; Laguna, Theresa A.; Heltshe, Sonya; Goss, Christopher H.; Sanders, Don B.; Pediatrics, School of Medicine
    Background: Cystic fibrosis (CF) is an autosomal recessive disease characterized by chronic sinopulmonary symptoms and chronic gastrointestinal symptoms that begins in infancy. Children with CF are increasingly being included in clinical trials. In order to fully evaluate the impact of new therapies in future clinical trials, an understanding of baseline adverse event (AE) rates in children with CF is needed. To address this, we determined the rates of common AEs in pediatric patients with CF who participated in two clinical trials. Methods: We reviewed AEs for placebo recipients in the AZ0004 study and inhaled tobramycin recipients in the Early Pseudomonas Infection Control (EPIC) clinical trial. AEs were categorized based on Medical Dictionary for Regulatory Activities (MedDRA) coding classifications and pooled into common, batched AE descriptors. AE rates were estimated from negative binomial models according to age groups, severity of lung disease, and season. Results: A total of 433 children had 8,266 total AEs reported, or 18.1 (95% CI 17.0, 19.2) AEs per person per year. Respiratory AEs were the most commonly reported AEs, with a rate of 7.6 events per person-year. The total SAE rate was 0.33 per person per-year. Cough was the most commonly reported respiratory AE, with 61% of subjects reporting at least one episode of cough within 4 months. The rate ratio of any AE was higher in Spring, Fall, and Winter, compared with Summer. Conclusions: AEs occur commonly in pediatric CF clinical trial participants. Season of enrollment could affect AE rates.
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    Study design considerations for the Standardized Treatment of Pulmonary Exacerbations 2 (STOP2): A trial to compare intravenous antibiotic treatment durations in CF
    (Elsevier, 2018-01) Heltshe, Sonya L.; West, Natalie E.; VanDevanter, Donald R.; Sanders, D. B.; Beckett, Valeria V.; Flume, Patrick A.; Goss, Christopher H.; Pediatrics, School of Medicine
    BACKGROUND: Pulmonary exacerbations (PEx) in cystic fibrosis (CF) are common and contribute to morbidity and mortality. Duration of IV antibiotic therapy to treat PEx varies widely in the US, and there are few data to guide treatment decisions. METHODS: We combined a survey of CF stakeholders with retrospective analyses of a recent observational study of CF PEx to design a multicenter, randomized, prospective study comparing the efficacy and safety of different durations of IV antibiotics for PEx to meet the needs of people with CF and their caregivers. RESULTS: IV antibiotic duration was cited as the most important PEx research question by responding CF physicians and top concern among surveyed CF patients/caregivers. During PEx, forced expiratory volume in 1s (FEV1% predicted) and symptom responses at 7-10days of IV antibiotics identified two distinct groups: early robust responders (ERR) who subsequently experienced greater FEV1 improvements compared to non-ERR (NERR). In addition to greater FEV1 and symptom responses, only 14% of ERR patients were treated with IV antibiotics for >15days, compared with 45% of NERR patients. CONCLUSIONS: A divergent trial design that evaluates subjects' interim improvement in FEV1 and symptoms to tailor randomization to IV treatment duration (10 vs. 14days for ERR, 14 vs. 21days for NERR) may alleviate physician and patient concerns about excess or inadequate treatment. Such a study has the potential to provide evidence necessary to standardize IV antibiotic duration in CF PEx care -a first step to conducting PEx research of other treatment features.