Chinese Medicine on Deferring Dialysis Initiation

Chinese Medicine (CM) treatment has been applied to CKD patients commonly in China, especially those independent of dialysis. Based on the personal experience of experts from different areas in China, patients with stage 5 CKD have been treated with different formulations of herbs including Astragalus membranaceus (Huangqi), Codonopsis pilosula (Dangshen), Semen Cuscutae (Tusizi) and Radix et Rhizoma Rhei (Dahuang) etc. . Based on the Traditional Chinese Medicine theory and clinical practise, these herbal medicines help strengthening "spleen-kidney" and dispelling "turbidity" . To determine whether CM therapies including Chinese herbal formula, Chinese patent medicine via oral pattern and/or Colonic administration, will significantly defer dialysis initiation, we conduct the Chinese Medicine on Deferring Dialysis Initiation (C-MODDI) study. It's a multicenter, prospective, controlled trial, also an effectiveness study that are conducted in the "real world" of a variety of busy clinical practices, with heterogeneous interventions that are more representative of the general effectiveness of CM therapies.

• CM therapies (Drug), also known as Traditional Chinese medicine (TCM) treatment, TCM treatment, Complementary Therapies: The choice of CM patterns will be at the treating physician's discretion. The dosing regimen of Chinese herbs and Chinese patent medicine will be as per the 2010 Chinese pharmacopoeia.The oral Chinese herbal formula will be composed of 18 herbs:Radix Astragali, Radix Codonopsis, Rhizoma Atractylodis Macrocephalae, Rhizoma diosscoreae, Poria, Semen Cuscutae, Radix Morindae Officinalis, Herba Epimedii, Herba Cistanches, Fructus Ligustri Lucidi, Rhizoma Polygonati, Fructus Amomi, Herba Agastaches, Rhizoma Coptidis, Radix et Rhizoma Rhei, Semen Coicis, Radix Salviae Miltiorrhizae, and stir-baked Semen Persicae. The Chinese herbal formula via Colonic administration will be composed of 3 herbs: Radix et Rhizoma Rhei, Calcined Concha Osterae, Herba Taraxaci.
• CKD-related management (Drug), also known as modern medicine, Western medicine: Western medicine treatment for CKD are practised following KDIGO and KDOQI guidelines, to reach the recommended goals of nutrition, blood pressure, hemoglobulin, electrolytes, fluid control and acid-base balance.

Primary outcomes

• Time to initiation of dialysis from enrollment. [From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.]: Averaged time from enrollment to dialysis initiation or death from any cause, whichever comes first. Patients commence dialysis based on the following criteria: 1. Clinical indications of dialysis include medically refractory serum potassium> 6.5mmol/L, total carbon dioxide (TCO2) <13mmol/L, eGFR≤5ml/min/1.73m2 (calculated by EPI formula), or the patient is symptomatic (see criteria #2). If these indications remain occur after receiving conservative CKD-related management for 1 week, or if relapse twice within one month, the patient definitely reaches the endpoint. 2. Uremic symptoms include nausea, vomit, malnutrition, pericarditis or pleurisy, volume overload, encephalopathy, bleeding tendency, refractory hypertension, or other symptoms that are likely to be ameliorated by dialysis.

Secondary outcomes

• all-cause mortality [From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.]: percentage of subjects who die from any cause during follow-up.
• Cardio-cerebro vascular events [From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.]: Cardio-cerebro vascular events, i.e. cerebral hemorrhage, cerebral infarction, myocardial infarction, acute coronary syndrome, severe arrhythmia, acute heart failure, acute exacerbation of congestive heart failure.
• Hospitalization or death caused by severe infection. [From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.]: percentage of subjects who suffer from severe infection events before dialysis initiation.The severe infection will lead to hospitalization or death. Infection events refer to death or hospitalization due to infection.
• incidence of severe adverse event/reaction [From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.]: number of cases of any recorded severe adverse event/reaction per year. Any adverse events/reactions complained of by patients or observed by researchers should be recorded, as well as any newly accompanied disease or aggravation of original symptoms.
• Slope of reciprocal serum creatinine [From date of enrollment until the date of first dialysis or date of death from any cause,or the end of study, whichever come first.The duration of follow up will be for a maximum of 4 years.]: Reciprocal serum creatinine (1/SCr) slope,the serum creatinine was assessed every 2 months.
• Nutrition and microinflammation status [From date of enrollment until the date of death from any cause,or the end of study, whichever come first, performed every 6 months.The duration of follow up will be for a maximum of 4 years.]: Malnutrition Inflammation Score is used to assess nutrition and microinflammation status.

Other outcomes

• Liver function [From date of enrollment until the date of death from any cause,or the end of study, whichever come first, performed every 6 months.The duration of follow up will be for a maximum of 4 years.]: aspartate aminotransferase (AST),alanine aminotransferase (ALT)
• Complete blood count [From date of enrollment until the date of death from any cause,or the end of study, whichever come first, performed every 6 months.The duration of follow up will be for a maximum of 4 years.]: Complete blood count
• Routine stool test + occult blood [From date of enrollment until the date of death from any cause,or the end of study, whichever come first, performed every 6 months.The duration of follow up will be for a maximum of 4 years.]: Routine stool test + occult blood
• Electrocardiogram [From date of enrollment until the date of death from any cause,or the end of study, whichever come first, performed every 6 months.The duration of follow up will be for a maximum of 4 years.]: Electrocardiogram
• Adverse event/reaction [From date of enrollment until the date of death from any cause,or the end of study, whichever come first, performed every 6 months.The duration of follow up will be for a maximum of 4 years.]: number of cases of any recorded adverse event/reaction per year.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Aged 18-75 years;
* with an estimated glomerular filtration rate (eGFR) between 5.5-15 ml/min per 1.73 m2;
* Non-diabetic CKD, which should be identified by biopsy or patients' medical histories.
* East Asian.

Exclusion Criteria:

* Clinical indications of dialysis still occur after conservative kidney management for 1 week, which will be ruled out as hemoglobin < 70g/L; or serum potassium> 6.5mmol/L; or Carbon Dioxide Combining Power (CO2CP) <13mmol/L; or EPI-GFR≤5ml/min/1.73m2 ;
* Pregnant or lactating.
* Critical status, such as alimentary tract hemorrhage or decompensated cirrhosis;
* History of malignancy other than a successfully and completely treated carcinoma;
* Any condition (mental or physical) that would interfere with the patient's ability to comply with the study protocol;
* Concurrent or current treatment with glucocorticoid or immunosuppressant agents in last 3 months;
* Participation in any other clinical trial;
* Known or suspected allergy to certain agents involved;

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• Xusheng Liu, MD, Study director, Guangdong Provincial Hospital of Traditional Chinese Medicine
• Ping Li, PhD, Principal investigator, China-Japan Friendship Hospital