How we can bulk up randomized control trials in peritoneal dialysis

Constipation is one of the most common and clinically significant complications in patients undergoing PD. It is highly prevalent^1,2 and has important clinical consequences. Distended bowel loops may compress or displace the PD catheter, leading to catheter flow dysfunction and inadequate dialysis. ³ Constipation has also been associated with an increased risk of peritonitis, likely related to bacterial translocation from the intestine.^1,4 In addition, it may contribute to the accumulation of uremic toxins, impaired ultrafiltration, abdominal hernias, and reduced quality of life.^4,5 Evidence from the Thailand PDOPPS cohort has even demonstrated an association between self-reported constipation and all-cause mortality. ¹ Compounding these risks, PD patients have been shown to have chronically inadequate dietary fiber intake, a consequence of dietary restrictions including fluid and competing nutritional priorities such as elevated protein requirements. ⁶ Emerging evidence suggests that fiber supplementation may have benefits beyond just stool bulking, reducing circulating uremic toxins and intraperitoneal inflammatory markers.^7,8

Despite its prevalence and clinical consequence, the level of evidence for constipation management in PD patients has been lacking, consisting primarily of observational studies, single-arm prospective trials, and expert opinion rather than high-quality randomized controlled trials.^9,10 This evidence gap is not unique to constipation: the majority of active ISPD guidelines at the time of this writing recommendations carry only Grade C or D evidence or are ungraded. It is against this background that the FIBRE-PD trial, a pilot randomized controlled study, offers a timely provocation: are our current standard-of-care laxatives failing our patients, and is it time to return to basics with natural fiber? The FIBRE-PD trial reported by Howard and colleagues in this issue of Peritoneal Dialysis International is significant not only for what it found but also for what its existence represents: a field moving to a higher evidentiary standard. ¹¹

In FIBRE-PD, the primary goal was to assess the feasibility of transitioning patients from the osmotic laxative Movicol to natural psyllium husk. While the study fell short of its recruitment target of 60 participants, the reason for this “failure” is perhaps the most illuminating finding of all. A staggering 62% of ineligible patients were excluded because they were already nonadherent to their prescribed Movicol. This high rate of nonadherence highlights that the current strategies are too burdensome, too expensive, or simply unpalatable for long-term use. This is not a failure of psyllium husk; it is a failure of our current standard of care to serve patients adequately. Among those who did enroll and receive psyllium husk, the picture was encouraging: retention of 77%, adherence of 78% by conventional definition, and effectively 100% when corrected for dose self-titration, no adverse events, significant reductions in global and physical distress scores on the Edmonton Symptom Assessment, and a trend toward reduced gastrointestinal symptom burden. These are meaningful signals in a population of just 18 analyzable participants.

This brings us to the deeper question the trial raises: how do we design peritoneal dialysis trials that are large enough to answer the questions that matter? The starting point is to recognize what FIBRE-PD was built to do. As a pilot randomized trial, it was designed to test whether a definitive trial of that question could be run at all, for example, whether eligible patients can be recruited, randomized, retained, and kept adherent to their assigned strategy. ¹² The natural evolution or next step requires multicenter collaboration, which the authors explicitly call for. The research community's obligation is to ensure that the call is answered with resources, not merely with acknowledgment. Beyond scale, FIBRE-PD also invites us to reconsider how we define eligibility in peritoneal dialysis trials. The requirement that participants be currently adherent to prescribed Movicol was logical from a methodological standpoint, as you need a comparator group, but it inadvertently excluded the very patients most in need of an alternative. Future trials might consider adaptive eligibility criteria or designs that enroll patients irrespective of prior laxative adherence and randomize them across a broader range of bowel management strategies. Pragmatic trial designs may also be particularly well suited to a condition as prevalent and heterogeneous as constipation in peritoneal dialysis. It is also worth considering the role of patient-reported outcomes and shared decision-making in future trial design. The FIBRE-PD trial's use of the Edmonton Symptom Assessment Scale is commendable, as it centers the patient experience rather than relying solely on surrogate endpoints like stool frequency. PD patients live with their therapy daily, and interventions that improve subjective well-being may drive adherence in ways that clinician-selected endpoints fail to capture. Future trials should continue to center the patient experience.

Randomized controlled trials in peritoneal dialysis have historically been rare. The FIBRE-PD, in its modest ambition and careful execution, demonstrates both the feasibility and the necessity of doing better. It also serves as a reminder that the barriers to better evidence aren’t solely scientific but logistical, financial, and cultural. Funding bodies must recognize that small, pragmatic trials in PD are not lesser science; they are the foundation upon which clinical practice in this field will either be built or continue to drift on expert opinion alone. Bulk up the trials, and we may yet bulk up the evidence base that patients on peritoneal dialysis deserve.