Clinical trial NCT03239808: Incremental Haemodialysis in Incident Patients
Official title: Assessment of the Incremental Haemodialysis Security and Effectiveness in Incident Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Renal Disease, End-Stage
Keywords: once-weekly haemodialysis
incremental haemodialysis
randomized clinical trial
Lead sponsor: Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura
Sponsor class: OTHER
Collaborators: name: Hospital Arquitecto Marcide. Ferrol. A Coruña. (Spain)
name: Hospital San Pedro de Alcantara
name: Virgen del Puerto Hospital
name: Hospital Central de la Defensa Gómez Ulla. Madrid (Spain)
name: Hospital Costa del Sol
name: Hospital Obispo Polanco. Teruel (Spain)
name: Hospital de Manises. Valencia (Spain)
name: Hospital Virgen de la Concha. Zamora (Spain)
name: Hospital de Especialidades de las Fuerzas Armadas. Quito (Ecuador)
name: Servicio Extremeño de Salud (Spain)
name: Hospital del SAS de Jerez
name: Hospital Nuestra Sra de Sonsoles. Ávila (Spain)
name: Dialysis Center SM2. Potenza (Italy)
name: Miulli General Hospital
name: Hospital del Rio Hortega
name: Hospital Duran de Buenos Aires
name: Hospital El Bierzo
name: Hospitales Universitarios Virgen del Rocío
name: Hospital Universitario Virgen Macarena
name: Hospital Universitario Dr J Trueta
First posted: 2017-08-04
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, multicenter, randomized clinical trial. It has two strata: for age (≥or\< 75 years old) and for KrU (≥or\< 5,5 ml/min/1.73m2). It is controlled through usual clinical practice.

Intervention consists in reducing the frequency or number of sessions per week with which patients start the HD treatment. The experimental group will start with one session/week, then the number of weekly sessions will be increased to two and later to three as per criteria for progression.
Primary purpose: TREATMENT

Brief summary: Background: Incremental hemodialysis (HD) is a starting regime for renal replacement therapy (RRT) adapted to each patient's necessities. It is mainly conditioned by the residual renal function (RRF). The frequency of sessions with which patients start HD -one or two sessions per week-, is lower than that for conventional HD three times per week. Such frequency is increased (from one to two sessions, and from two to three sessions) as the RRF declines.

Methods/Design: IHDIP is a multicenter randomized experimental open trial. It is randomized in a 1:1 ratio and controlled through usual clinical practice, with a low intervention level and non-commercial. It includes 152 patients older than 18 years with chronic renal disease stage 5 and start HD as RRT, with a RRF of ≥ 4ml/min/1.73m2, measured by renal clearance of urea (KrU). The intervention group includes 76 patients who will start with one session of HD per week (incremental HD). The control group includes 76 patients who will start with three sessions per week (conventional HD). The primary purpose is assessing the survival rate, while the secondary purposes are the morbidity rate (hospital admissions), the clinical parameters, the quality of life and the efficiency.

Discussion: This study will enable us to know with the highest level of scientific evidence, the number of sessions a patient should receive when starting the HD treatment, depending on his/her RRF.

Detailed description: Conventional thrice-weekly HD for 3 to 5 hours in a health center in an outpatient basis is the most used renal replacement therapy (RRT) regimen (1). However, it has an unacceptable high mortality rate (10%-20% a year). In order to try to improve those results, new regimens have been proposed. They are based on an increase of the HD dose and/or a higher number of sessions (2). Nevertheless, inconsistent results in terms of clinical benefits with such programs have been shown in recently published randomized and controlled trials (3,4), together with a lower rate of vascular access success (5) and a lower maintenance of the RRF (6) The National Kidney Foundation-Kidney Disease Outcomes Quality Initiate (NKD KDOQI 2015)(1) 2015 guidelines allow the reduction in the weekly HD dose for patients with a residual kidney urea clearance (KrU) higher than 3ml/min/1.73m2. In these cases, the renal clearance (Kr) is added to the dialysis clearance (Kd) obtained in 2 sessions per week, thus obtaining the adequate dialysis dose (7,8) Surprisingly enough, few centers follow this recommendation when over 50% of patients start HD with KrU \>3 mL/min (9).

Authors like Kalantar-Zadeh et al (9,10) in the U.S.A. or Teruel et al (11) in Spain have published their experience with 2 HD sessions per week in incident patients. Through this regime they have shown that the RRF is preserved and the survival rate is similar to the one obtained with the conventional HD. This is due to the fact that the Kr has much greater clinical weight than Kd7, since the RRF contributes to the production of vitamin D and erythropoietine (12,13), and eliminates the protein-bound uremic toxins that are poorly dialyzed (13,14). In other words, the RRF plays a fundamental role both in the dialysis adequacy and in survival (15,16).

Currently, some authors are questioning the number of HD sessions with which a patient should start the renal replacement therapy (RRT) (7, 17-19). Progressive HD is an initiation regimen adapted to the patient's RRF. The frequency increases as the daily diuretic level declines (7, 17-19).

The IHDIP trial20 aims at determining whether or not starting with one HD session per week reduces mortality in incident patients and its influence in morbidity (hospital admissions), clinical parameters, quality of life and efficiency with regard to the patients who start RRT with the conventional method.

Eligibility criteria: Inclusion Criteria:

* Adults aged \>18 years, incident patients with stage 5 CKD who have chosen HD as RRT initiation.
* RRF measured by KrU ≥ 4 ml/min/1.73m2. In general, it is advised not to start HD with a KrU\> 7.
* Informed consent signed before starting any activity related to the trial.

Exclusion Criteria:

* Unplanned HD initiation (established in point 7.4 of the protocol)
* Non incident patients, in other words, patients who were previously on RRT, either on peritoneal dialysis, or on kidney transplant.
* Active neoplasia at the moment of inclusion
* Cardiovascular disease defined as: heart failure type IV of the New York Heart Association (NYHA), unstable angina or ischemic cardiopathy which has caused any admission in hospital in the last 3 months.
* Cardiorenal syndrome
* Active inflammatory disease with immunosuppressive treatment
* Hepatorenal syndrome

Primary outcomes:
measure: Survival rate
timeFrame: 24 months
Secondary outcomes:
measure: Hospital admissions
timeFrame: 24 months
measure: Residual Kidney Function (RRF) maintenance .
timeFrame: 24 months
measure: Analysis of anemia
timeFrame: 3, 6, 9, 12, 18 and 24 months
measure: Bone-mineral metabolism
timeFrame: 3, 6, 9, 12, 18 and 24 months
measure: Hypertrophic cardiomyopathy levels
timeFrame: Basal, anual and end of the follow-un visit
measure: Estimation of the effect of treatment on quality of life
timeFrame: 3, 6, 9, 12, 18 and 24 months
measure: Assessing RRT efficiency (costs)
timeFrame: 12 and 24 months
Other outcomes:
Locations:
city: Mérida
country: Spain
facility: FundeSalud. Junta de Extremadura
state: Badajoz
city: Plasencia
country: Spain
facility: Hospital Virgen del Puerto
state: Cáceres
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
Study officials:
affiliation: Servicio Extremeño de Salud
name: Javier L Deira Lorenzo, PhD MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Servicio Extremeño de Salud
name: Miguel A Suarez Santisteban, MD
role: PRINCIPAL_INVESTIGATOR
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