Rectal indomethacin administered for 48 hours in patients with acute pancreatitis (AP) and systemic inflammatory response syndrome (SIRS) was safe but not superior to placebo in reducing SIRS score or preventing clinical progression of AP, according to a study in Clinical and Translational Gastroenterology.
This randomized placebo-controlled trial was conducted at an urban university medical center. Eligible patients were those aged ≥18 years who were admitted with AP and had SIRS within 72 hours of initial presentation to the emergency department.
Participants were randomly assigned 1:1 to either rectal indomethacin or placebo. Those in the intervention arm received a loading dose of two 50-mg indomethacin suppositories rectally administered, followed by five 50-mg maintenance doses at 8-hour intervals for 6 total doses. Those in the placebo arm received glycerin suppositories at similar intervals.
The primary end point was change in SIRS score from randomization to 48 hours after the initial intervention.
A total of 42 patients were randomly assigned to indomethacin (n=18) or placebo (n=24). Participants had a mean age of 51.5±19.5 years, 54.8% were men, 83.3% were White, and the median duration of symptoms before presentation was 12 hours (IQR, 3.8-20.0 hours).
The change in SIRS scores 48 hours from randomization was comparable in patients who received indomethacin (-1.0±1.24) and in those who received placebo (-0.96±0.81) (P =.87). No significant differences were observed in change in SIRS score from randomization to 24 hours (P =.16) and to 72 hours (P =.72) between the 2 groups.
SIRS was present in a similar proportion of participants at 24 hours (indomethacin 88.9% vs placebo 70.8%; P =.26), 48 hours (61.1% vs 62.5%, respectively; P =1.00), and 72 hours (44.4% vs 50%, respectively; P =.72).
The distribution of SIRS scores (0-4) was not significantly different in the 2 groups at 24 hours (P =.34), 48 hours (P =.24), or 72 hours (P =.90). No significant differences were observed between treatment groups regarding mean C-reactive protein (CRP) levels at 48 hours (P =.70) and in the change in CRP levels at 48 hours (P =.48).
The 2 treatment arms had similar rates of moderately severe AP (indomethacin 50% vs placebo 54.2%) and severe AP (16.7% vs 12.5%) (P =1.00).
No adverse events occurred in the indomethacin group, and 2 occurred in the placebo group.
The investigators noted that their pilot study was not powered to detect a difference in major clinical outcomes, and thus a type 2 error is possible. Additionally, they included only patients with AP and SIRS from a single tertiary care center.
“Future investigations should focus on the efficacy of [nonsteroidal anti-inflammatory drugs] when administered earlier in the disease course (within 12-24 hours from presentation) before SIRS onset,” the study authors stated.
Machicado JD, Mounzer R, Paragomi P, et al. Rectal indomethacin does not mitigate the systemic inflammatory response syndrome in acute pancreatitis: a randomized trial. Clin Transl Gastroenterol. 2021;12(11):e00415. doi: 10.14309/ctg.0000000000000415