Wireless pH-motility capsule for colonic transit: prospective comparison with radiopaque markers in chronic constipation

Abstract

Background: Colon transit (CT) measurements are used in the management of significant constipation. The radiopaque marker (ROM) method provides limited information.

Methods: We proposed to validate wireless motility capsule (WMC), that measures pH, pressure and temperature, to ROM measurement of CT in patients with symptomatic constipation evaluated at multiple centers. Of 208 patients recruited, 158 eligible patients underwent simultaneous measurement of colonic transit time (CTT) using ROM (Metcalf method, cut off for delay >67 h), and WMC (cutoff for delay >59 h). The study was designed to demonstrate substantial equivalence, defined as diagnostic agreement >65% for patients who had normal or delayed ROM transit.

Key results: Fifty-nine of 157 patients had delayed ROM CT. Transit results by the two methods differed: ROM median 55.0 h [IQR 31.0-85.0] and WMC (43.5 h [21.7-70.3], P < 0.001. The positive percent agreement between WMC and ROM for delayed transit was approximately 80%; positive agreement in 47 by WMC/59 by ROM or 0.796 (95% CI = 0.67-0.98); agreement vs null hypothesis (65%) P = 0.01. The negative percent agreement (normal transit) was approximately 91%: 89 by WMC/98 by ROM or 0.908 (95% CI = 0.83-0.96); agreement vs null hypothesis (65%), P = 0.00001. Overall device agreement was 87%. There were significant correlations (P < 0.001) between ROM and WMC transit (CTT [r = 0.707] and between ROM and combined small and large bowel transit [r = 0.704]). There were no significant adverse events.

Conclusions & inferences: The 87% overall agreement (positive and negative) validates WMC relative to ROM in differentiating slow vs normal CT in a multicenter clinical study of constipation.

Trial registration: ClinicalTrials.gov NCT00857363.

Figure 1

Consort flow chart of participants in study: 208 patients enrolled in the study with 158 successfully completing the study with analyzable data. The 5 subjects who were not compliant failed to attend the study site for the required abdominal radiograph for ROM transit measurement.

Figure 2

CTT and SLBTT by WMC and colonic transit time by ROM in the entire patient cohort with evaluable data. Data show median, interquartile range (box), 5–95 percentile (whiskers) and outliers as individual points. Note that, while there is clear overlap between the data by each method of transit estimation, the paired analysis shows significant differences in the WMC estimates for CTT (p<0.001) and SLBTT (p=0.013, Wilcoxon Signed Rank Test) relative to the ROM estimated colonic transit time. For reference purposes, note that 95^th percentiles in healthy controls are 67 hours for ROM transit, 59 hours for CTT, and 65 hours for SLBTT.

Figure 3

Relationship between CTT and SLBTT by WMC and colonic transit time by ROM (at day 4 plus 7) in the entire patient cohort with evaluable data. Note the significant correlations between WMC estimates and ROM transit time. Interrupted line shows the 95% CI around the regression line. The shaded areas show the values at and above the 95^th percentiles for the different methods: 67 hours for ROM transit, 59 hours for CTT, and 65 hours for SLBTT.