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CompletedNCT03385902ADIFEUpdated May 8, 2026

Assessment of Dialysis Initiation by a Fuzzy Mathematics Equation

An interventional study of optimal start time and late start time in Chronic Kidney Disease, sponsored by The First Affiliated Hospital of Dalian Medical University. Completed at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-05-08.

Sponsored by The First Affiliated Hospital of Dalian Medical University · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
388
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate the impact of the optimal and late initiation of dialysis on the mortality and quality of life in end-stage renal disease (ESRD) patients by the Dialysis Initiation based on Fuzzy mathematics Equation (DIFE), which is a novel equation for the assessment of timing of dialysis initiation established by Fuzzy mathematics.

Read the detailed description

The optimal time of dialysis initiation is still controversial. Estimated glomerular filtration rate (eGFR) which is now widely used as the assessment of timing of dialysis is lack of specificity. Some clinical factors such as heart failure, volume overload, malnutrition also determine the dialysis time. But these subjective judgements do not have a standard. So there is no quantitative assessment of timing of dialysis initiation. The research team developed a novel equation named DIFE (Dialysis Initiation based on Fuzzy mathematics Equation) with data from a retrospective multicenter cohort by fuzzy mathematical methods to combine these clinical factors and lab indexes. The DIFE was confirmed to be more accurate and convenient to use in clinical practice than eGFR only at the assessment of dialysis initiation time in the internal validation. For further validation of the DIFE, the team will conduct a multicenter randomized controlled trial. Patients who need hemodialysis will be randomized to optimal start dailysis group or late start dailysis group by the assessment of the DIFE. Based on the comparison of the two groups, this trial will provide evidence for the optimal timing of dialysis initiation in patients with end-stage renal disease by the DIFE.

02

Conditions studied

  • Chronic Kidney Disease

Keywords

  • end-stage renal disease
  • timing of dialysis initiation
  • hemodialysis
  • fuzzy mathematics
  • glomerular filtration rate
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Have progressive chronic kidney disease with an eGFR less than 15 ml/min/1.73m2 and a DIFE between 30-35
  • Expected to commence maintenance hemodialysis as their renal replacement treatment
  • Agreeable to randomization

Exclusion criteria

Exclusion Criteria:

  • Acute kidney injury (AKI) or AKI on chronic kidney disease (CKD)
  • With the primary disease of systemic lupus erythematosus (SLE) or systemic vasculitis
  • Have received or planning to receive a kidney transplant or peritoneal dialysis during the study
  • Has a recently diagnosed cancer that was likely to affect survival (except for the following cases: the cancer has been confirmed to be cured or relieved for over 5 years, have had the radical resection for the basal cell carcinoma or squamous carcinoma of skin or carcinoma in-situ of any part of the body )
  • Hepatocirrhosis
  • Positive test of Human Immunodeficiency Virus (HIV), the hepatitis B virus antigen (HBsAg) or anti-hepatitis C virus antibody (HCV Ab)
  • Acute infection within 1 month
  • Bad habit which is difficult to withdrawal such as alcohol abuse
  • Poor compliance and could not be treated according to the protocol
  • Being pregnant, nursing or having a plan for pregnancy
  • Life expectancy less than 1 year
  • The investigator confirm that should not enroll in the study with any other cases
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
388 participants (actual)

Study arms

  • Experimental
    optimal start dialysis group

    The DIFE will be used as the assessment of initiation time of dialysis. Patients in this group will start dialysis when their results of the DIFE reaching to 30-35, which defined as the optimal start time.

    Other: optimal start time

  • Active comparator
    late start dialysis group

    the DIFE will be used as the assessment of initiation time of dialysis. Patients in this group will start dialysis when their results of the DIFE less than 30, which defined as late start time.

    Other: late start time

Interventions

  • Otheroptimal start time

    patients will start hemodialysis when their DIFE reach 35, and can not wait if the DIFE decline to 30.

  • Otherlate start time

    patients will start hemodialysis when their DIFE less than 30

05

What researchers measure

Primary outcomes

  1. all-cause mortality

    proportion of patients who die from any cause

    Time frame: from the date of enrollment until the end of study, assessed up to 3 years

  2. cerebro-cardiovascular mortality

    proportion of patients who die from cerebro-cardiovascular disease

    Time frame: 3 years, from the date of enrollment until the end of study

Secondary outcomes

  1. cerebro-cardiovascular events

    proportion of patients who suffer from cardiovascular events, which include nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack,new-onset angina, acute heart failure or severe arrhythmia.

    Time frame: from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years

  2. hospitalization

    proportion of patients admitted to hospital

    Time frame: from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years

  3. Nutrition assessment

    assess the patient's nutritional status by subjective global assessment (SGA) assessment and serum albumin level

    Time frame: from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years

  4. the change of quality of life

    use short form-36 reported by the patients to assess the patient's quality of life

    Time frame: from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years

  5. Medical cost

    the cost by the patient, family and insurance during treatment

    Time frame: from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years

  6. Hemodialysis complications

    the proportion of patients who suffer from hemodialysis complications including blood assess revise, assess infection, severe fluid and electrolyte disorders

    Time frame: from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years

  7. cognitive dysfunction

    assess cognitive dysfunction by Montreal Cognitive Assessment (MoCA)

    Time frame: from the date of enrollment until the date of death from any cause, or the end of study, which ever came first, assessed up to 3 years

06

Study locations

1 site
  • the First Affiliated Hospital of Dalian Medical University
    Dalian, Liaoning 116011, China
07

References and documents

Publications

  • Cooper BA, Branley P, Bulfone L, Collins JF, Craig JC, Fraenkel MB, Harris A, Johnson DW, Kesselhut J, Li JJ, Luxton G, Pilmore A, Tiller DJ, Harris DC, Pollock CA; IDEAL Study. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010 Aug 12;363(7):609-19. doi: 10.1056/NEJMoa1000552. Epub 2010 Jun 27. PubMed 20581422 ↗
  • Crews DC, Scialla JJ, Boulware LE, Navaneethan SD, Nally JV Jr, Liu X, Arrigain S, Schold JD, Ephraim PL, Jolly SE, Sozio SM, Michels WM, Miskulin DC, Tangri N, Shafi T, Wu AW, Bandeen-Roche K; DEcIDE Network Patient Outcomes in End Stage Renal Disease Study Investigators. Comparative effectiveness of early versus conventional timing of dialysis initiation in advanced CKD. Am J Kidney Dis. 2014 May;63(5):806-15. doi: 10.1053/j.ajkd.2013.12.010. Epub 2014 Feb 6. PubMed 24508475 ↗
  • Susantitaphong P, Altamimi S, Ashkar M, Balk EM, Stel VS, Wright S, Jaber BL. GFR at initiation of dialysis and mortality in CKD: a meta-analysis. Am J Kidney Dis. 2012 Jun;59(6):829-40. doi: 10.1053/j.ajkd.2012.01.015. Epub 2012 Apr 1. PubMed 22465328 ↗
  • Nesrallah GE, Mustafa RA, Clark WF, Bass A, Barnieh L, Hemmelgarn BR, Klarenbach S, Quinn RR, Hiremath S, Ravani P, Sood MM, Moist LM; Canadian Society of Nephrology. Canadian Society of Nephrology 2014 clinical practice guideline for timing the initiation of chronic dialysis. CMAJ. 2014 Feb 4;186(2):112-7. doi: 10.1503/cmaj.130363. No abstract available. PubMed 24492525 ↗
  • Sood MM, Komenda P, Rigatto C, Hiebert B, Tangri N. The association of eGFR reporting with the timing of dialysis initiation. J Am Soc Nephrol. 2014 Sep;25(9):2097-104. doi: 10.1681/ASN.2013090953. Epub 2014 Mar 20. PubMed 24652801 ↗
  • Hwang SJ, Yang WC, Lin MY, Mau LW, Chen HC; Taiwan Society of Nephrology. Impact of the clinical conditions at dialysis initiation on mortality in incident haemodialysis patients: a national cohort study in Taiwan. Nephrol Dial Transplant. 2010 Aug;25(8):2616-24. doi: 10.1093/ndt/gfq308. Epub 2010 Jun 2. PubMed 20519231 ↗
  • Chen J, Liu Y, Chen X, Sun X, Li W, Yang W, Li P, Sun X, Wang D, Jiang H, Shi W, Liu W, Fu P, Ding X, Chang M, Liu S, Yang X, Cao N, Chen M, Ni Z, Chen J, Sun S, Liang X, Wang H, He Y, Gao B, Wang J, Hao L, Liu J, Li S, He Q, Liu H, Yi N, Shao F, Jiao J, Ma Y, Yao L, Sun Y, Li D, Szczech L, Fang M, Odeh Z, Lin H. Assessment of dialysis initiation by a fuzzy mathematics equation (ADIFE): a study protocol for a randomised controlled trial. BMJ Open. 2019 Sep 8;9(9):e023162. doi: 10.1136/bmjopen-2018-023162. PubMed 31501092 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03385902
Lead sponsor
The First Affiliated Hospital of Dalian Medical University
Collaborators
Chinese PLA General Hospital, Fudan University, RenJi Hospital, Beijing Friendship Hospital, Huashan Hospital, West China Hospital, First Affiliated Hospital, Sun Yat-Sen University, Chinese Academy of Medical Sciences, Fuwai Hospital, First Affiliated Hospital of Harbin Medical University, The Second Affiliated Hospital of Harbin Medical University, General hospital of benxi iron and steel co., Dalian Municipal Central Hospital, An Steel Group Hospital, The First Affiliated Hospital of the Fourth Military Medical University, General Hospital of Mining Industry Group Fuxin, Affiliated Zhongshan Hospital of Dalian University, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University, General Hospital of Ningxia Medical University, Lanzhou University Second Hospital, First Affiliated Hospital of Xinjiang Medical University, First Hospital of China Medical University, Central Hospital Affiliated to Shenyang Medical Collage, First Affiliated Hospital Xi'an Jiaotong University, Henan Provincial People's Hospital, Guangdong Provincial People's Hospital
Responsible party
Lin Hongli (Director of Nephrology Department, The First Affiliated Hospital of Dalian Medical University, The First Affiliated Hospital of Dalian Medical University) — Principal investigator
First posted
Dec 29, 2017
Start date
Apr 14, 2018
Primary completion
May 20, 2024
Completion
May 20, 2024
Last update
May 8, 2026

Study contacts

Hongli Lin, MD, PhD
study director · The First Affiliated Hospital of Dalian Medical University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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