Budesonide versus placebo in high-risk population with screen-detected lung nodules: rationale, design and methodology.
BACKGROUND
Screening-CT is able to discover small peripheral lung nodules. The nature of these nodules is uncertain but it is reasonable that some of them, in particular the non-solid ones, could represent precancerous lesions. A previous trial showed a reduction in size of peripheral nodules by inhaled budesonide in subjects with bronchial dysplasia.


OBJECTIVE
The primary objective of the study was the evaluation of the effect of budesonide as a chemopreventive agent for lung lesions. The primary endpoint was the modification of lung lesions at ld-CT scan (according to RECIST criteria) after one year of treatment in a person-specific analysis.


METHODS
We performed a randomized, double-blind, placebo controlled trial to evaluate whether inhaled budesonide was able to reduce size and number of persistent, undetermined CT-detected lung nodules in high-risk asymptomatic subjects currently undergoing a five-year CT scan screening program at the European Institute of Oncology.


RESULTS
Trial enrollment started in April 2006 and ended in July 2007 with the randomization of 202 current or former smokers with stable CT-detected lung nodules set to receive budesonide 800 μg or placebo twice daily for 12 months.


CONCLUSIONS
Our trial represents the first phase II study of a chemopreventive intervention focusing on the peripheral lung, where the majority of lung cancers arise. The research was nested into a screening project with clear advantages in participant accrual and reduction of costs. This paper describes the rationale and design of the study, thus focusing on the methodology and operational aspects of the clinical trial. (Clinicaltrials.gov number. NCT00321893).
Lazzeroni
Matteo
M
Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy. matteo.lazzeroni@ieo.it
Guerrieri-Gonzaga
Aliana
A
Serrano
Davide
D
Varricchio
Maria Clara
MC
Veronesi
Giulia
G
Radice
Davide
D
Feroce
Irene
I
Nardi-Pantoli
Angela
A
Lippman
Scott M
SM
Szabo
Eva
E
Bonanni
Bernardo
B
D000280:Administration, Inhalation; D000465:Algorithms; D019819:Budesonide / Q000627:therapeutic use*; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D055613:Multiple Pulmonary Nodules / Q000000981:diagnostic imaging / Q000188:drug therapy*; D012107:Research Design; D018401:Sample Size; D014057:Tomography, X-Ray Computed
D005938:Glucocorticoids; D019819:Budesonide