The ACTIVE Trial: Defining duration of Dialysis Outcomes

By Peter Laird, MD

The debate over the efficacy of increased frequency or duration of dialysis compared to the now standard in-center schedules is an unsettled issue despite over 600 observational studies in the last 50 years showing the benefits of more frequent and longer duration dialysis. Performing randomized and controlled trials of increased frequency and duration is plagued by recruitment issues where many patients who are candidates to participate instead decline the 50% chance of remaining in-center on thrice weekly dialysis. To date, we have only two RCT's on daily or longer duration dialysis, the FHN and the nocturnal studies by Culleton, et al .  The FHN showed a clear benefit to more frequent short daily dialysis strategies.  The nocturnal study showed a significant improvement in LVH among daily nocturnal dialysis patients.

The issue of longer duration dialysis remains unsettled in the eyes of many academic nephrologists because the nocturnal arm of the FHN failed to achieve a high enough statistical  power due to severe recruitment issues. Fortunately, there is another ongoing study called the ACTIVE Trial that will evaluate whether patients do better with more than 24 hours/week of dialysis or less than 18 hours/week.

A Clinical Trial of IntensiVE Dialysis (ACTIVE)

A rapidly increasing volume of observational data suggests substantial benefits may be associated with an increased duration of dialysis. As well as improved quality of life, improved functioning and beneficial changes in a variety of laboratory parameters, it has been suggested that extended dialysis sessions might reduce mortality and major morbidity. Uncontrolled data from centres that have been providing extended dialysis shows dramatically lower mortality rates compared to those observed in centres providing standard duration dialysis. Recent analyses of extended dialysis conclude that the savings achieved in drug and hospitalization costs may lead to an overall reduction in costs compared with traditional forms of dialysis.

In this trial, we propose to examine the effects of extended dialysis (24 hours weekly or more) compared to standard dialysis (18 hours or less weekly) in patients with ESKD. The proposed study is a multi-centre, open label, randomised, controlled trial.

The study began with a pilot phase which was converted to the current main study on the receipt of peer-reviewed funding for the full study.

I personally believe we no longer have equipoise to perform further dialysis studies on the frequency and duration of dialysis protocols, yet those that make the decisions on payment for dialysis in America continue to seek the evasive holy grail of randomized and controlled dialysis trials. Fortunately, if they successfully recruit the expected number of patients, the ACTIVE trial may answer the last remaining issue before the dialysis community on whether longer duration dialysis strategies have a significant clinical benefit.  Should the ACTIVE trial show the expected benefit of longer duration dialysis as seen in the many observational studies, we will simply be where we were nearly 50 years ago when the pioneers of dialysis settled on a minimum of 24 hours of dialysis a week to rehabilitate their patients.  It is time to return to our roots and re-institute longer duration and more frequent dialysis as the standard dialysis therapy in America.  Only then will we begin the journey to true renal rehabilitation.

 

Comments

[MooseMom]

I think you got it, Peter...those that make the decisions re: payment are going to keep "studying" the efficacy of more frequent dialysis into the next decade. Does anyone really doubt that more dialysis leads to a better outcome?

[MooseMom]

Peter, we keep being told that there are not enough RCTs to support the idea that more dialysis more frequently is superior to standard D. Were there historically ever any RCTs done that supposedly established in-center HD as superior treatment? How was that 3xweekly protocol decided upon? Was it purely financial, or was there any medical evidence that showed this modality to be a good one? Thanks.

[Peter Laird, MD]

Dear MooseMom, in answer to your question, in short, NO, they did not do a RCT of thrice weekly extended duration dialysis vs what was in the 1970's termed "ultra-short" hemodialysis of 4 hours until the ill fated nocturnal arm of the FHN commenced. Neither have they ever compared transplant against optimal dialysis in an RCT. The only people required to prove the observational studies by an RCT are those that support more frequent and longer duration strategies. It is a unique double standard.

[MooseMom]

And that's the answer I expected...!