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Randomized Controlled Trial
. 2010 Mar;45(3):291-300.
doi: 10.1002/ppul.21179.

Lessons learned from a randomized trial of airway secretion clearance techniques in cystic fibrosis

Marci K Sontag  1 , Alexandra L Quittner, Avani C Modi, Joni M Koenig, Don Giles, Christopher M Oermann, Michael W Konstan, Robert Castile, Frank J Accurso; Investigators and Coordinators of the Airway Secretion Clearance Trial
Collaborators, Affiliations
Randomized Controlled Trial

Lessons learned from a randomized trial of airway secretion clearance techniques in cystic fibrosis

Marci K Sontag et al. Pediatr Pulmonol. 2010 Mar.

Abstract

Rationale: Airway secretion clearance therapies are a cornerstone of cystic fibrosis care, however longitudinal comparative studies are rare. Our objectives were to compare three therapies [postural drainage and percussion: (postural drainage), flutter device (FD), and high frequency chest wall oscillation: (vest)], by studying (1) change in pulmonary function; (2) time to need for intravenous (IV) antibiotics, (3) use of pulmonary therapies, (4) adherence to treatment, (5) treatment satisfaction, and (6) quality of life.

Methods: Participants were randomly assigned to one of three therapies twice daily. Clinical outcomes were assessed quarterly over 3 years.

Results: Enrollment goals were not met, and withdrawal rates were high, especially in postural drainage (51%) and FD (26%), compared to vest (9%), resulting in early termination. FEV(1) decline, time to need IV antibiotics, and other pulmonary therapies were not different. The annual FEF(25-75%) predicted rate of decline was greater in those using vest (P = 0.02). Adherence was not significantly different (P = 0.09). Overall treatment satisfaction was higher in vest and FD than in postural drainage (P < 0.05). Health-related quality of life was not different. The rate of FEV(1) decline was 1.23% predicted/year.

Conclusions: The study was ended early due to dropout and smaller than expected decline in FEV(1). Patients were more satisfied with vest and FD. The longitudinal decline in FEF(25-75%) was faster in vest; we found no other difference in lung function decline, taken together this warrants further study. The slow decline in FEV(1) illustrates the difficulty with FEV(1) decline as a clinical trial outcome.

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Figures

Figure 1
Figure 1
Flow diagram of patient enrollment, randomization and retention. * Eleven of the participants who withdrew in the first 60-days withdrew on the day of randomization
Figure 2
Figure 2
Box and Whisker Plot of days of study participation. Whiskers denote minimum and maximum observations, box signifies 25th percentile, median, and 75th percentile with mean represented by a ⊕. Open squares represent observations beyond 1.5 × the interquartile range (IQR). Box width varies with number of observations. Panel a: participants who withdrew prior to study termination. Panel b: participants who remained in the trial until study termination.
Figure 3
Figure 3
Cross Sectional depiction of mean pulmonary function results (bars indicate 95% confidence interval, 1.96*SEM). Panel a: FVC % Predicted; Panel b: FEV1 % Predicted, Panel c: FEF 25–75% % predicted.
Figure 4
Figure 4
Modeled longitudinal decline in pulmonary function (plotted for BMI=50th percentile).

  1. Panel a: FVC % Predicted

    1. PD&P: y=85.1 (± 2.7 SEM) − 1.5 (± 0.94) *years in study + 0.13*BMI%

    2. FD: y=85.6 (± 2.8 SEM) − 1.7 (± 0.89) *years in study + 0.13*BMI%

    3. HFCWO: y=84.2 (± 2.7 SEM) − 0.32 (± 0.77 SEM) *years in study + 0.13*BMI%

    4. p=NS, comparison of all slopes

  2. Panel b: FEV1 % Predicted

    1. PD&P: y=80.3 (± 3.6 SEM) − 1.0 (± 0.96) *years in study + 0.14*BMI%

    2. FD:: y=82.3 (± 3.7 SEM) – 1.9 (± 0.91) *years in study + 0.14*BMI%

    3. HFCWO: y=80.4 (± 3.5 SEM) – 1.20 (± 0.78 SEM)*years in study + 0.14*BMI%

    4. p=NS, comparison of all slopes

  3. Panel c: FEF 25–75% % Predicted

    1. PD&P: y=71.2 (± 4.7 SEM) + 0.85 (± 0.99) *years in study

    2. FD: y=71.1 (± 4.7 SEM) – 0.16 (± 0.90) *years in study

    3. HFCWO: y=73.1 (± 4.3 SEM) – 2.32 (± 0.76 SEM) *years in study

    4. p=0.01 PD&P vs HFCWO, p=0.035 FD vs. HFCWO

Figure 5
Figure 5
Time to need IV antibiotics. Open circles are censored observations (patient withdrew or study terminated at that point).
Figure 6
Figure 6
Percent adherence as measured through daily phone diaries across each of the first 5 assessment points. Differences in mean adherence were found as follows: Assessment #2: FD compared to PD&P (p=0.005), Assessment #3: FD compared to PD&P (p=0.006) and FD compared to HFCWO (p=0.003), and Assessment #4: FD compared to HFCWO (p=0.04).
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