Clinical trial NCT02933151: Health Effects of oraL Protein Supplements in HD (The HELPS-HD Trial)
Official title: Health Effects of oraL Protein Supplements in HD (The HELPS-HD Trial) An Open-Label Cluster Randomized Pragmatic Trial Evaluating the Effectiveness of Oral Intradialytic Nutritional Supplements on Mortality in Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Renal Disease
Lead sponsor: Dialysis Clinic, Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-14
Enrollment: 10457
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: To conduct a pragmatic randomized clinical trial in which the researchers will determine the mortality impact of a protocol whereby all hemodialysis patients receive an oral, protein-based nutritional supplement during the dialysis procedure as compared to the existing nutritional protocol whereby only hemodialysis patients with serum albumin below 3.5 g/dL and incident hemodialysis patients during the first months of care receive an oral, intradialytic protein-based nutritional supplement during the dialysis procedure.

Detailed description: HELPS-HD is a pragmatic, cluster randomized clinical trial comparing the effectiveness of two different oral nutritional supplement protocols and accompanying education. All participants in participating facilities will be asked to participate in the study unless they do not qualify. Reflecting the pragmatic study design targeting broad generalizability, inclusion criteria are broad and exclusions are minimal.

The trial compares Usual Care versus an Intensive Nutritional Supplement Protocol. Facilities are cluster randomized into one of two protocols:

1. Usual care protocol which will continue the current nutritional supplement protocol for all patients at the dialysis facility, whereby those with albumin below 3.5 g/dL receive supplement
2. Intensive nutritional supplement protocol, which will prescribe nutritional supplements for all patients at the dialysis facility regardless of serum albumin levels

The majority of DCI facilities currently have the majority of their patients prescribed the usual care oral nutritional supplement protocol, with 20-30% of patients at any given time receiving an in-center oral nutritional supplement based on either incident hemodialysis status or low serum albumin. Of note, all patients are offered the protocol, but approximately 10-20% refuse the protein supplement, often due to taste and individual preference. Being prescribed the protocol does not affect a patient's ability to consume food or other supplements of their choosing before, during (depending on facility and state regulations) or after dialysis; it simply means that they receive an oral nutritional supplement for consumption during dialysis from the dialysis facility included as a part of their routine dialysis care. The specific nutritional supplement is not specified in the protocol, although many facilities currently use Prostat due to pricing and availability. The protocol prescribes approximately 15 g of oral protein supplement; when Prostat is used, this is accomplished by drinking 30 mL of Prostat. In cases of facility or patient preference, including taste fatigue, other supplements can be used in the current usual care protocol in lieu of Prostat. For example, the PI's facility currently has some patients receiving Prostat while others receive BodyQuest Protein Ice Cream, reflecting patient preference. Nutritional supplements utilized during the trial will vary, but should contain approximately 15 g (range 12 to 20 g) of protein with low sodium, potassium and phosphorus content. Based on current use within DCI and availability as well as prior experiences and cost, the following supplements are anticipated:

1. BodyQuest Protein Ice Cream, which contains 16 g of protein and 120 kcal per serving
2. Prostat, Sugar Free, which contains 15 g of protein and 100 kcal per serving
3. LiquaCel Liquid Protein, which contains 16 g of protein and 90 kcal per serving
4. ZonePerfect Nutrition Bars ( flavor varied to avoid taste fatigue), which contain \~ 15 g of protein and \~ 210 kcal per serving
5. Nepro, which contains 19 g of protein and 425 kcal per serving.

As occurs currently in practice, the serum albumin level from routinely drawn monthly labs will automatically feed into the electronic centralized nutritional supplement prescribing protocols, from which supplements are then prescribed and administered. The DCI electronic oral nutritional supplement protocol will be used in the same manner as in current practice and follow the same rules for dosing and stoppage for the usual care arm, while protocol-based administration will continue regardless of serum albumin level for the intensive protocol arm. All new patients at the time of dialysis initiation (first dialysis session) will receive an oral nutritional supplement if prescribed the protocol by their physician, regardless of intensive or usual care protocol assignment based on their facility. The specific supplement is typically based upon what the individual facility has available and on storage space within facilities. For example, one supplement is a frozen protein supplement (BodyQuest Protein Ice Cream) that can only be used in facilities that have adequate space for food freezers.

As a non-blinded study, the treating physicians will be aware of the study allocation of the facility. In facilities assigned to the intensive oral nutritional supplement intervention, an order will be generated in the DCI MIS by DCI Information Services for administration of an oral protein supplement at each dialysis session. Similarly, in patients assigned to the standard oral nutritional supplement intervention, a renewal order of the current supplement protocol will be generated. As with all orders pertaining to in-center hemodialysis care, the order for intensive versus standard nutritional supplement protocol will need to be signed electronically by the physician caring for the patient. If the physician does not sign this order, the patient will not receive nutritional supplements. The physician, regardless of randomization, can elect to discontinue the supplement order at any time.

As is currently done in practice, the dialysis nurse will record in the treatment record that the nutritional supplement has been dispensed and whether and when it was consumed. Supplements should be distributed and consumed within the first 30 minutes of initiation of a dialysis session.

Within all facilities, patients will receive information regarding the nutritional supplement trial. Educational posters will be displayed in public waiting areas, including signs and posters that inform patients that the site is participating in the trial as well as signs and posters that promote the importance of nutrition and adequate protein intake in recipients of hemodialysis. Every dialysis facility, as a condition for coverage by CMS, is required to have a dietician who provides nutritional information to patients. Regardless of randomization assignment, this individual will continue to encourage appropriate protein intake for dialysis patients, including recommendations for protein and other hemodialysis-appropriate diet consumption at home.

Facilities randomized to usual care and to intensive supplements will have slightly different approaches. First, facilities randomized to the usual care arm will have different signs and posters than those randomized to the intensive arm. Usual care arm materials will promote the need for nutrition and encourage supplement consumption when the albumin is low. Patients are informed of their serum albumin levels monthly at dialysis when they receive feedback from the dietician. In these conversations, the dietician will continue to emphasize protein consumption as per prior routine. For intensive facilities, materials will focus on the catabolic stresses induced by dialysis regardless of baseline albumin level, and emphasize that oral nutritional supplements taken early during dialysis may be able to impact catabolism. Reflecting the open nature of dialysis facilities, if neighboring patients are on different treatment regimens, they are likely to overhear the specific counseling given to other patients and are likely to appreciate that others are receiving more or less supplements than they are. Finally, there is a group mentality prevalent among dialysis patients such that they expect to receive similar treatment and interventions. These factors reinforce the hemodialysis environment as best suited to cluster randomization.

Eligibility criteria: Inclusion Criteria:

1. Receipt of in-center hemodialysis in a facility participating in the trial
2. Able to consume oral nutritional supplements
3. Age ≥18 years

Exclusion Criteria:

1. Tube feed or intravenous feed dependent
2. Unable to feed oneself or request help with feeding if a supplement is provided
3. Known allergy to ingredient(s) of the supplement

Primary outcomes:
measure: Mortality
timeFrame: Intervention discontinued on April 13, 2020 due to Covid-related prohibition on eating in facilities. Event follow-up concluded on August 13, 2020. Follow-up time varied among participants, with the maximum of approximately 3.5 years.
Secondary outcomes:
measure: Hospitalization
timeFrame: Median 7.1 months (25th to 75th percentile: 3.0, 10.9 months)
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: DCI Jacksonville
state: Florida
city: Nashville
country: United States
facility: Dialysis Clinic, Inc (Corporate)
state: Tennessee
Study officials:
affiliation: DCI/Tufts
name: Daniel Weiner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mah JY, Choy SW, Roberts MA, Desai AM, Corken M, Gwini SM, McMahon LP. Oral protein-based supplements versus placebo or no treatment for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2020 May 11;5(5):CD012616. doi: 10.1002/14651858.CD012616.pub2.