Sirs, We read with interest Mikhailova et al.’s publication regarding the efficacy of propionyl-L-carnitine (PLC) in ulcerative colitis (UC).1 This multi-centre, double-blind trial concluded that PLC was a potential treatment for the management of UC, based on an improved clinical/endoscopic response (disease activity index improvement of three or more), compared with placebo.1 There are, however, some limitations of the trial that warrant further discussion.
First, subjects within the study underwent colonoscopy and biopsies at baseline and again after 4 weeks of treatment. Histological grading revealed that 23 (19%) patients had no significant active inflammation at baseline, which was reported as a “minor protocol violation”. This seems rather concerning, given that close to a fifth of the participant’s within the trial may not have had active UC.
Secondly, the power calculation for the study was based on a placebo response rate of 10%, whereas meta-analyses of treatment trials in UC reveal placebo remission rates of 13–21%, and response rates of up to 40%.2, 3 Presumably as a result of this, the study was not powered to detect statistically significant differences in many of the endpoints the authors reported, and therefore no reliable conclusions can be drawn.
Thirdly, the trial reported a significant clinical/endoscopic response in those participants who received PLC 1 g/day compared with placebo; but there was no statistical improvement in patients given PLC 2 g/day. It was suggested that this was a result of saturation at the point of uptake. If this were the case, participants on 2 g/day would have a response equal to those on 1 g/day.
Fourthly, it was of interest that the investigators had to extend the recruitment to centres outside of Italy. This may be a consequence of their decision to perform repeat colonoscopy as the endoscopic test of choice at baseline and week 4, when perhaps sigmoidoscopy would have been more acceptable to patients and of equal diagnostic benefit.
In summary, whilst the data were interesting, we believe that the efficacy of this compound in inducing remission in mildly to moderately active UC remains unclear.