Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03415776 |
| Other study ID # |
TATH2018 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 16, 2018 |
| Est. completion date |
October 25, 2022 |
Study information
| Verified date |
October 2022 |
| Source |
Saint-Joseph University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Hemodialysis is the most worldwide prescribed renal replacement therapy for patients with
end-stage renal disease. The frequency of sessions per week remains a debatable issue. In the
majority of developed Western and Asian countries, patients on chronic hemodialysis are
undergoing three dialysis sessions weekly. In developing countries and some developed
countries, a twice-weekly schedule independent of residual kidney function is still accepted,
sometimes because of lack of resources and some other times because of patients' resistance
to undergo three sessions per week. The primary objective of this trial is to assess the
total mortality of patients on thrice against twice-weekly hemodialysis. The secondary
objectives are a) to compare the rate of urgent supplementary hemodialysis sessions between
the two arms, mainly those due to pulmonary edema and hyperkalemia, b) to compare the number
of hospitalizations and duration of stay, c) to compare the rate of uncontrolled hypertension
between the two groups, d) to analyze the quantity of erythropoiesis-stimulating agents
(ESAs) in units to achieve a haemoglobin (Hb) 11 to 11.5 g/dl, e) to assess the factors
associated with a higher mortality in the two groups.
Description:
Hemodialysis (HD) is the most worldwide prescribed renal replacement therapy for patients
with end-stage renal disease. This treatment that relies heavily on technology has undergone
major modifications in the last five decades in order to improve patients' outcomes. Those
changes that aimed at reducing the morbidity and mortality of patients targeted mainly the
water purification system, the membrane's permeability and biocompatibility, the dialysate
composition and the dose of hemodialysis. However, the frequency of sessions per week remains
a debatable issue influenced by the fluctuating scientific evidence and the patient's
disapproval of being increasingly dependent on a machine.
In the majority of developed Western and Asian countries, patients on chronic hemodialysis
are undergoing three dialysis sessions weekly.
In 2007 the European guidelines recommended the thrice-weekly hemodialysis with a session
duration 3-5 hours. This dose of treatment will ensure hemodialysis sessions adequacy defined
as urea reduction ratio >65% . However thrice-weekly hemodialysis has been established
worldwide without randomized clinical trials. The rationale behind the thrice-weekly dialysis
seems to be the uncertainty about dialysis adequacy and the risk of malnutrition, anemia and
intra-dialytic hypotension with twice-weekly sessions. Several cohorts have also shown a
favorable effect on survival with thrice compared to twice-weekly hemodialysis especially
when duration of treatment per week of the twice-weekly schedule was less than 8 hours.
Incremental hemodialysis is defined as starting dialysis twice weekly for those who have a
substantial renal urea clearance and switching after 3 months to three times weekly. A large
retrospective study from the US showed that incremental hemodialysis compared to conventional
hemodialysis (three times per week) improved mortality in those with a renal urea clearance
>=3 ml/min/1.73 m2 or urine volume > 600 ml/day. The rationale behind the incremental
schedule is that preserving residual kidney function would lead to better outcomes. However
based on this incremental method, patients should be watched closely for the residual kidney
function and switched at the right moment to three sessions per week otherwise there will be
an overlap between the two phases and an information bias regarding the timing of residual
renal function loss.
In developing countries and some developed countries, a twice-weekly schedule independent of
residual kidney function is still accepted, sometimes because of lack of resources and some
other times because of patients' resistance to undergo three sessions per week. Several
studies have shown that patients on twice-weekly hemodialysis without residual kidney
function have a shorter survival than those on three times per week. A recent prospective
study from Korea showed that residual kidney function is not the only factor that would favor
thrice over twice weekly HD. Another retrospective Indian study showed similar mortality
between those on twice versus thrice-weekly HD while a Chinese observational study
demonstrated longer survival in anuric patients on twice- than thrice-weekly dialysis. All
these controversial studies make it unclear whether patients are still allowed to undergo
twice-weekly hemodialysis.
Lebanon is a developing upper middle-income country from the Eastern Mediterranean region
where around 3800 patients are undergoing chronic hemodialysis three or twice weekly.
Although the Lebanese Ministry of Public Health recommended in 2014 that all patients on
chronic hemodialysis be dialyzed three times weekly, many nephrologists are still allowing
the twice schedule if it is more convenient to the patients. With these circumstances,
Lebanon appears an attractive place to study the difference in outcomes between the two
hemodialysis schedules.
Trial design This is a non-randomized, multicenter, clinical trial. Randomization was
considered unethical and contradictory with the current international guidelines. Therefore
patient's allocation was left at the nephrologist and patient's agreement.
Crossover will be allowed during follow-up to limit attrition. This study will assess the
equivalence between the two schedules.
Methods: participants, interventions and outcomes
Study setting Hemodialysis patients will be recruited from multiple Lebanese HD centers.
Lebanon is divided into 9 governorates and includes 77 HD units. From each governorate 50% of
the units will participate in the trial.
Interventions Patients will be assigned to one of two groups upon their agreement with the
treating nephrologist: Group 1 will receive three sessions of hemodialysis weekly. Group 2
will receive two sessions weekly.
Participant timeline Recruitment of patients will be done over two years or until the
pre-determined sample size is reached whichever comes earlier.
Sample size Knowing that the proportion of death varies between 10% and 40%, if we consider a
two sided alpha of 5%, a power of 80% and a small effect size = 0.20 (Cohen's d), the total
sample size needed would be 806 patients. Assuming an attrition rate of 10%, we would need
806/0.9 = 896 patients. The representative sample size for this study is ~900 patients. 600
patients are necessary for the three times weekly arm and 300 patients for the twice weekly
arm.
Recruitment It may be difficult to reach 300 patients on twice weekly so the recruitment will
go on till this number is reached.
Methods: Data collection, management, and analysis
Data collection methods eCRF (electronic case report form) will be used for data capture.
Data for demographics, comorbidities, laboratory results, medications and dialysis
prescription will be collected from the patients' medical records at dialysis initiation.
The following variables will be studied:
Baseline characteristics: age, gender, body mass index (BMI), diabetes, smoking,
hypertension, hyperlipidemia, cause of end-stage renal disease (ESRD), previous
cardiovascular disease, atrial fibrillation, dementia, Laboratory: serum creatinine (with
corresponding estimated glomerular filtration rate (eGFR), phosphate, calcium, albumin,
potassium, sodium, bicarbonate, hemoglobin, parathyroid hormone (PTH), alkaline phosphatase,
ferritin, transferrin saturation, uric acid, hepatitis B (HBV) and hepatitis C (HCV)
serologies.
Residual renal function: Urine volume and renal urea clearance will be assessed at baseline
by collecting the 24 hour-urine at dialysis initiation.
Medications: statins, calcium-based and non-calcium-based phosphate binders, vitamin D,
antihypertensive medications, antiplatelet agents, erythropoiesis stimulating agents (ESA)
dose, renin-angiotensin system inhibitors, oral anticoagulants.
Dialysis prescription: Number of hours per week, blood flow, dialysate flow, type of vascular
access (catheter, graft or arteriovenous fistula), filter membranes (surface, low-flux or
high-flux), dialysate potassium and calcium content will be collected.
Definitions Chronic kidney disease stage 5 is defined as an eGFR <15 ml/min. Coronary artery
disease is defined as a history of myocardial infarction or obstructive coronary artery
disease, treated medically or interventionally. Diabetes and hypertension are defined as
having a history for antidiabetic or antihypertensive treatment respectively.
Uncontrolled hypertension is defined as a pre-dialysis BP > 160/90 in more than 2/3 of the
sessions. Residual kidney function is defined as a diuresis > 500 ml/d on a non-dialysis day.
Statistical analysis Continuous variables will be presented as mean ± standard deviation
(SD). Differences between the study groups will be tested using χ2 tests (for categorical
variables). Bivariate correlation analysis will be performed using the Pearson's correlation
coefficient. The Kaplan-Meier method will be used to estimate the cumulative survival. Cox
regression will be used to determine the effect of dialysis frequency and other covariates on
mortality. Analysis will be performed on an intention-to-treat basis. Statistical analysis
will be performed with SPSS. A P-value of ≤0.05 will be considered statistically significant.
Methods: Monitoring
Data monitoring Follow-up with laboratory measurements and medication dosage Every month:
hemoglobin, calcium, phosphorus, urea, creatinine, potassium, sodium, bicarbonate.
Every 4 months: PTH, ferritin, transferrin saturation. Every year: lipid panel, albumin. All
these biological parameters will be measured with the standard laboratory techniques and
medications adjusted to maintain serum calcium, phosphate and PTH within the target range.
Total ESA quantity used for each patient, as well as doses of alfacalcidol, cinacalcet,
phosphate binders and antihypertensive treatment will be collected every 3 months.
Clinical follow-up Data that will be collected monthly includes: mid-week pre-dialysis
systolic and diastolic blood pressure, average interdialytic fluid gain, number, causes
(myocardial infarction, angina, atrial fibrillation, pulmonary edema, hyperkalemia) and
length of hospital stay (LOS), residual kidney function, number of vascular access
thrombosis. Blood pressure will be recorded every week and presented as a monthly average.
