Fig 1.
a Refer to PAINLESS Study Timeline (Figure 2). b On-study clinical follow-up visits will occur as clinically indicated in clinic, the hospital or at home. c End-of-study visit will be the first clinical visit occurring > 9 months after the start of Observational Year 2. d Study personnel will continue to review NTM culture results and clinical events recorded in the CFFPR for up to 5 years following end of study. e Samples may be obtained in clinic, the hospital or at home, either expectorated or sputum induction. If results from oropharyngeal swab or bronchoscopy are available, they will also be recorded. f Urine sample must be collected within 30 days of a sputum sample at the start of Year 1 and Year 2. End-of-study urine sample does not need to be linked to a sputum sample. g Standard clinical assessments will be obtained from CFF patient registry database. h Replacement urine for LAM assay if needed.
Fig 2.
PAINLESS study design and timeline: Panel
A: Screening criteria requires no history of NTM positive cultures combined with at least 3 negative sputum cultures for NTM over the past 3 years. Panel B: At enrollment, the first urine sample for LAM analysis is collected and is within 30 days of a NTM sputum culture. It is anticipated that a positive urine LAM will be detected in a subset of subject, who will comprise a “high risk cohort” that is more likely to have a positive NTM sputum culture. Panel C: Over the course of the study, NTM sputum cultures will be obtained when available in the context of clinical care. Panel D: At the end of Year 1, a second urine will be collected for LAM analysis. It is anticipated that some subjects with negative LAM at enrollment will convert to positive at each follow-up interval, and likewise some subjects with positive LAM at enrollment will convert to negative. Panel E: At the end of the second year of observation a 3rd urine sample will be collected for LAM analysis, as well as sputum for NTM culture (if available). Panel F: Results from future sputum NTM cultures will be monitored from the CFF Patient Registry for up to 5 years following the end of study procedures.
Table 1.
Inclusion and exclusion criteria of the painless trial.
Fig 3.
Representative GC/MS chromatograms showing the absence and/or presence of urinary LAM related to NTM-negativity and/or positivity.
A) D-Arabinose (D-ara) MS/MS method monitoring m/z 420.9-m/z 192.9): Four characteristic peaks of Internal Standard (13C5-D-Arabinose; top panel); Sequentially (top to bottom), 309 and 308 NTM negative, D-ara negative; BP201 and 303 are positive, LAM positive, NTM positive. B) Tuberculostearic acid (TBSA) Single ion monitoring (SIM) at m/z 297.3: TBSA standard (C:19; top panel); Sequentially, 309 and 308 NTM negative, TBSA negative; BP201 and 303 are TBSA positive, LAM positive, NTM positive..