Routine and Deferred Dialysis Initiation

Study Overview
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Brief Summary
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This study evaluates the efficacy and safety of deferred dialysis initiation in Chinese population. 16 tertiary hospitals across China will be randomly assigned into routine and deferred dialysis groups.

Detailed Description
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The timing for initiating dialysis for progressive chronic kidney disease (CKD) patients is an important issue yet is not well established. There is a strong trend to early dialysis initiation for end stage renal disease (ESRD) patients over the past decades. However, observational data found that early initiation seemed to produce no benefit but additional burden to patients and the health care system. The IDEAL study, the only randomized, controlled trial (RCT) on this issue, found that all-cause mortality, comorbidities and quality of life had no difference between early (glomerular filtration rate, GFR 10-14ml/min/1.73m2) and late (GFR 5-7ml/min/1.73m2) dialysis starters. However there was a big limitation in this study that the difference for average GFR between two groups (12 ml/min/1.73 m2 vs. 9.8 ml/min/1.73m2) was not so separate. Recently, the Canadian Society of Nephrology have released a clinical practice guideline on this issue. The guideline recommends an intent-to-defer approach for dialysis initiation and to initiate dialysis in the absence of symptoms in patients with an estimated GFR of 6 ml/min /1.73 m2 or less. In this guideline the specialists also express that the optimal management of patients with an estimated GFR of 6 ml/min per 1.73 m2 or less is based on limited data. There is a gap in knowledge. This research will further evaluate the efficacy and safety of deferred dialysis initiation and fill in this gap. In this study, algorithms will be adopted to determine the timing of dialysis initiation for both routine and deferred dialiysis groups, and the only difference in these two algorithms is the GFR level to initiate dialysis (7 Vs. <5 ml/min per 1.73 m2). The theory that blood access (arteriovenous fistulas) can be timely prepared according to the past GFR decline trajectory will also be tested.

Official Title
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A Randomized, Controlled Trial to Evaluate Routine and Deferred Dialysis Initiation in Chinese Population

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Other: Algorithm for deferred dialysis intervention
* Other: Algorithm for routine dialysis intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nondialysis-dependent stable CKD stage 4-5 patients (eGFR>7ml/min /1.73 m2) Willing to choose dialysis as his renal replacement therapy method Heart function: grade I or II (NYHA Functional Classification) Exclusion Criteria: The life expectancy of patients is estimated to be short (due to causes other than kidney disease); Acute infection occurred in one month; Myocardial infarction, NYHA class IV or stroke events within 3 months; Uncontrolled malignancy; Active viral hepatitis; Active rheumatic disease; Pregnant women, women intending to conceive after enrollment or breastfeeding woman; Planning to take kidney transplantation within the study period; With indices of emergency dialysis; eGFR less than 7 ml/min/1.73m2 in first visit; Under other clinical studies which has an impact on this study; Unable to provide written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deffered Dialysis Initiation<br>Algorithm for deferred dialysis intervention: initiating dialysis in the absence of symptoms in patients with an eGFR of 5 ml/min /1.73 m2 or less | Other: Algorithm for deferred dialysis intervention<br>* Use combined indications to guide researchers to defer dialyzing progressive CKD patients. Asymptomatic patient will not start dialysis treatment until his eGFR becomes less than 5 ml/min/1.73m2. Or until 1. Patient's Kraemer index is >6 or with overt fluid overload after trying all conservative means（including appropriate medicines） 2. Patient's Subjective Global Assessment method (SGA) assessment is grade C 3. Patients have indications for emergency dialysis 4. Sever symptoms which cannot be relieved by conservative treatment<br>|
| Active Comparator: Routine dialysis Initiation<br>Algorithm for routine dialysis intervention: initiating dialysis in the absence of symptoms in patients with an eGFR of 7 ml/min /1.73 m2 (which is the average GFR for patients in Beijing to start dialysis ) | Other: Algorithm for routine dialysis intervention<br>* Use combined indications to guide researchers to initiate dialysis in progressive CKD patients routinely. Researchers will start dialysis treatment for a patient when his eGFR reaches 7 ml/min/1.73m2 in asymptomatic patients. Or patients have indications below: 1. Patient's Kraemer index is >6 or with overt fluid overload after trying all conservative means（including appropriate medicines） 2. Patient's SGA assessment is grade C 3. Patients have indications for emergency dialysis 4. Sever symptoms which cannot be relieved by conservative treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality: Proportion of patients who die from any cause | Proportion of patients who die from any cause during observation period. | From date of enrollment until the end of study, assessed up to 3 years | 
| Acute nonfatal cerebro-cardiovascular events before dialysis initiation | Proportion of patients who suffer from acute nonfatal cerebro-cardiovascular events before dialysis initiation. Cerebro-cardiovascular events include acute myocardial infarction,acute coronary ischemia syndrome,acute heart failure, acute exacerbation of chronic heart failure ,severe arrhythmia, stroke, etc. | From date of enrollment until the date of dialysis initiation, or the date of death from any cause,or the end of study, whichever came first, assessed up to 3 year | 
| Acute nonfatal cerebro-cardiovascular events after dialysis initiation | Proportion of patients who suffer from acute nonfatal cerebro-cardiovascular events after dialysis initiation. Cerebro-cardiovascular events include acute myocardial infarction,acute coronary ischemia syndrome,acute heart failure, acute exacerbation of chronic heart failure ,severe arrhythmia, stroke, etc. | From date of dialysis initiation until the date of death from any cause,or the end of study, whichever came first, assessed up to 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalization: Proportion of patients who are admitted to hospital | Proportion of patients who are admitted to hospital | From date of enrollment until the date of death from any cause,or the end of study, whichever came first, assessed up to 3 year | 
| Nutrition assessment | SGA assessment and serum albumin level are used to assess nutrition status | From date of enrollment until the date of death from any cause,or the end of study, whichever came first, assessed up to 3 years, performed every 3 months | 
| Patient reported outcome of quality of life | The short form health survey questionnaire 36 will be used. | From date of enrollment until the date of death from any cause,or the end of study, whichever came first, assessed up to 3 years, once every 3 months | 
| Complications of dialysis | Proportion of patients who suffer from dialysis complications including blood acess infection, thrombosis, hypotension, etc. | From date of dialysis initiation until the date of death from any cause,or the end of study, whichever came first, assessed up to 3 year | 
| Costs | All money patients and insurance agency spend on medical care related with CKD | From date of enrollment until the date of death from any cause,or the end of study, whichever came first, assessed up to 3 years, performed every 3 months | 
| Arteriovenous fistulas usage | Proportion of patients using arteriovenous fistulas as their blood access when dialysis initiation. The timing for preparing arteriovenous fistulas depends on the past GFR decline trajectory | From date of enrollment until the date of dialysis initiation, assessed up to 3 years | 
| Catheter usage | Proportion of patients using catheter as their blood access when dialysis initiation. | From date of enrollment until the date of dialysis initiation, assessed up to 3 years |