Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials.

BACKGROUND: Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI). METHODS: The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEV1 (ppFEV1) of 70% or more, or those aged 18 years or older with ppFEV1 of 60% or more, if they had been taking ETI and either (or both) mucoactive therapies (≥3% hypertonic saline or dornase alfa) for at least 90 days before screening. Participants on both hypertonic saline and dornase alfa were randomly assigned to one of the two trials, and those on a single therapy were assigned to the applicable trial. All participants were then randomly assigned 1:1 to continue or discontinue therapy for 6 weeks using permuted blocks of varying size, stratified by baseline ppFEV1 (week 0; ≥90% or <90%), single or concurrent use of hypertonic saline and dornase alfa, previous SIMPLIFY study participation (yes or no), and age (≥18 or <18 years). For participants randomly assigned to continue their therapy during a given trial, this therapy was instructed to be taken at least once daily according to each participant's pre-existing, clinically prescribed regimen. Hypertonic saline concentration was required to be at least 3%. The primary objective for each trial was to determine whether discontinuing was non-inferior to continuing, measured by the 6-week change in ppFEV1 in the per-protocol population. We established a non-inferiority margin of -3% for the difference between groups in the 6-week change in ppFEV1. Safety outcomes were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04378153. FINDINGS: From Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEV1 of 96·9%. Discontinuing treatment was non-inferior to continuing treatment with respect to the absolute 6-week change in ppFEV1 in both the hypertonic saline trial (-0·19% [95% CI -0·85 to 0·48] in the discontinuation group [n=133] vs 0·14% [-0·51 to 0·78] in the continuation group [n=140]; between-group difference -0·32% [-1·25 to 0·60]) and dornase alfa trial (0·18% [-0·38 to 0·74] in the discontinuation group [n=199] vs -0·16% [-0·73 to 0·41] in the continuation group [n=193]; between-group difference 0·35% [-0·45 to 1·14]), with consistent results in the intention-to-treat populations. In the hypertonic saline trial, 64 (35%) of 184 in the discontinuation group versus 44 (24%) of 186 participants in the continuation group and, in the dornase alfa trial, 89 (37%) of 240 in the discontinuation group versus 55 (23%) of 237 in the continuation group had at least one adverse event. INTERPRETATION: In individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.

Understanding Treatment Adherence With the Health Belief Model in Children With Cystic Fibrosis.

OBJECTIVE: Children's health beliefs are significantly related to their adherence; however, pediatric literature has rarely tested health-related theories as a whole. The goal of the present study was to evaluate the use of the health belief model (HBM) in understanding children's adherence, both globally and to individual treatment components. METHOD: Thirty-three patient-parent dyads completed questionnaires regarding health beliefs and adherence to medical regimens. RESULTS: Multiple linear regressions found a significant relationship among the HBM variables and reports of global adherence for children and parents. For children, the HBM variables were significantly related to adherence to aerosol medications, aerosol antibiotics, metered dose inhalers, and vitamins. For parents, the HBM variables were significantly related to children's adherence to airway clearance, oral antibiotics, and vitamins. Paired sample t tests found children and parents had significantly discrepant heath beliefs. CONCLUSION: These findings provide further support for the HBM in evaluating pediatric adherence, with evidence that barriers and cues to action may be targets for early intervention. Future research using this model to identify a comprehensive way to assess, understand, and elicit change in the adherence to medical regimens for youth with chronic illness would be beneficial.

Impact of age and gender on adherence to infection control guidelines and medical regimens in cystic fibrosis.

RATIONALE: The goal of the present research was to examine the impact of age and gender on adherence to both infection control (IC) guidelines and traditional medical treatments in a cystic fibrosis (CF) population. Adherence behaviors are consistently suboptimal in chronic illness populations, particularly pulmonary diseases; understanding the factors related to adherence behaviors in CF can aid in the development of interventions to promote adherence. METHOD: Participants consisted of 74 individuals with CF ages 9 years and above. Participants were asked to complete questionnaires designed to assess demographic data, treatment adherence, and health beliefs. RESULTS: With respect to IC guidelines, chi-square analyses revealed significant age differences in adherence behaviors such that the young adult subsample was least adherent to IC (χ2 = 15.10, df = 6, P = 0.020). Next, a 4 (age: child, adolescent, young adult, adult) × 2 (gender) completely between subjects analysis of variance (ANOVA) was conducted on medical treatment adherence. There was a significant main effect for age [F(3, 65) = 2.940, P = 0.040, ηP2 = 0.119] indicating that the adolescent subsample had the most adherence challenges. Gender was nonsignificant across both adherence types. CONCLUSIONS: Study findings are suggestive of age-related differences in adherence behaviors across both IC and medical regimens and support the use of developmentally sensitive approaches to assessment and interventions addressing adherence.

Compliance in cystic fibrosis: an examination of infection control guidelines.

The goal of this research was to begin the process of evaluating acceptability of infection control (IC) recommendations to CF patients and their families, determine whether compliance with IC guidelines differs from compliance with traditional CF medical treatment with respect to the variables predictive of compliance, and assess which patients are most likely to comply with IC recommendations. Participants were recruited during routine outpatient visits at a regional CF center located in a pediatric hospital. The sample included 44 child and adolescent patients, aged 9-18 years and their guardian, and 27 adult patients. All patients completed questionnaires and interviews. Results of this preliminary study suggest that many individuals with CF are unaware of or unconcerned with the risks involved in infection transmission via social contact with other CF patients. Further, most participants reported that they could benefit from friendships with other CF patients. Health belief variables were found to be predictive of compliance with both IC guidelines and traditional medical treatments in the adult and parent sample, but not in the child sample. Possible explanations for study findings are discussed and recommendations for future research on IC compliance are highlighted.