Effectiveness of polaprezinc for low-dose aspirin-induced small-bowel mucosal injuries as evaluated by capsule endoscopy: a pilot randomized controlled study

Consecutive patients undergoing upper gastrointestinal endoscopy or colonoscopy at Hiroshima University Hospital and taking LDA between May 2010 and September 2011 were screened for inclusion in the study. These patients were visiting our hospital for endoscopic treatment of gastrointestinal tumor, follow-up endoscopic examination after endoscopic treatment, treatment of gastrointestinal bleeding outside the small intestine, or examination for obscure gastrointestinal bleeding (OGIB). Inclusion criteria were as follows: use of low-dose enteric-coated aspirin at 100 mg once daily for more than 3 months; no current use of antibiotics; age ≥ 21years; an initial CE examination. Exclusion criteria were as follows: use of NSAIDs other than LDA; inflammatory bowel disease; digestion-absorption disorder; polaprezinc treatment; use of other medicines for gastritis, e.g., misoprostol or rebamipide, within the prior 6 months; use of antibiotics or thyroxine sodium; stenosis of the gastrointestinal tract or severe adhesion; pregnancy or nursing; severe ulcerative lesion(s) observed upon initial CE, absence of small-bowel injury upon initial CE, and failure of the CE capsule to reach the cecum. Twenty patients in whom LDA-induced small-bowel injury was identified upon initial CE, as described below, comprised the final study group.

The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Hiroshima University Hospital. All patients screened for inclusion in the study were provided written informed consent for participation. The trial is registered with the UMIN Clinical Trials Registry as number UMIN000003687.

The 20 patients in whom LDA-induced small-bowel injury was identified during the screening process were randomized into two groups: a polaprezinc group (n = 10) and a control group (n = 10). For allocation of patients to the study groups, we followed a block randomization scheme. Patients were given their assignments in sealed envelopes that had been shuffled previously. Patients in the polaprezinc group were given polaprezinc at 150 mg daily for 4 weeks, whereas patients in the control group were not given polaprezinc during the 4-week period. All patients continued LDA at 100 mg daily. Initial CE was defined as CE performed at the time patients were first examined in our department; follow-up CE was performed after 4 weeks in both groups.

The CE capsule (PillCam SB2; Given Imaging Ltd, Yoqneam, Israel) was swallowed with a solution of dimethicone after an overnight fast, without any other preparation. Images were analyzed with Rapid Reader 6.5 software on a RAPID 6.0 workstation (both from Given Imaging). CE images were reviewed independently by two of four experienced gastroenterologists (I.W., T.A., H.I., T.S.) who were not provided any clinical information. If the gastroenterologists’ findings differed, consensus was reached through discussion.

NSAID-induced small-bowel injury is characterized by multiple petechiae/red spots, denuded area, scars, mucosal erosions, and ulcers with a round, irregular, or punched-out appearance, or circumferential ulcers with stricture [19]. Such LDA-induced small-bowel injury was diagnosed at the time of initial CE.

Small-bowel mucosal injuries were classified as either erosion/ulcer or reddened lesion [20, 21] as follows: erosion, a white spot surrounded by a red halo; ulcer, depression with a white coating; reddened lesion, reddish mucosal change such as reddened folds, denuded area, and/or petechiae (Figure 1); red spots were ignored in this study. LDA-induced small-bowel injuries were defined as follows; (1) ulcer, erosion or reddened lesion detected by capsule endoscopy, (2) use of LDA for more than 3 months, and (3) exclusion of Crohn’s disease, intestinal tuberculosis and any other small bowel disease.

We assessed the anatomic distribution of LDA-induced small-bowel mucosal injuries upon initial CE according to the following numerical formula based on capsule transit time through the small intestine [22]: Lesion location, i.e., first, second, or third portion of the small bowel corresponding to the percentage of total transit time, = (CE time when lesion is found – CE time of first duodenal image)/small bowel transit time.

To evaluate the effectiveness of polaprezinc, the number of small-bowel injuries and CE score [23] were calculated for each patient upon initial CE and upon follow-up CE. Changes in the number of small-bowel injuries and the difference in CE scores between initial CE and follow-up CE were compared between the polaprezinc group and the control group.

The CE score [23] was determined for small-bowel mucosal inflammatory changes. The score was based on three capsule endoscopy variables: villous appearance, ulceration, and stenosis. Severity of the mucosal inflammatory changes was assessed in tertiles by dividing small-bowel capsule transit time into three equal allotments. The total CE score was taken as the highest tertile score plus the stenosis score. The results were classified into three categories based on the final numerical score: normal or clinically insignificant change (total score <135), mild change (total score ≥135 but <789), and moderate to severe change (total score ≥790). This scoring system has been shown to be useful for evaluating aspirin-associated small-bowel mucosal disease activity and for objectively scoring the small-bowel inflammatory disease state [24].