Chinese Medicine on Deferring Dialysis Initiation

End-Stage Renal Disease Clinical Trial

— C-MODDI  

Official title:

Effectiveness of Chinese Medicine on Deferring Dialysis Initiation for Stage 5 Chronic Kidney Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02194946
• Other study ID #: 2013BAI02B04
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 2014
• Est. completion date: December 2020

Study information

• Verified date: December 2019
• Source: Guangdong Provincial Hospital of Traditional Chinese Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Stage 5 chronic kidney disease (CKD), also end stage renal disease(ESRD), usually presents overt clinical symptoms and is a critical stage when patients are encountered with dialysis. The optimal time to initiating dialysis in patients with stage 5 CKD is addressed as the most important dialysis-related question. As indicated by the recently published European Renal Best Practice (ERBP) guideline, early initiation seemed to produce no benefit but greater expenditure and sometimes more harm.Renal replacement therapies (RRT) including dialysis are the most common procedures for patients with end-stage renal disease (ESRD), but conservative management should be an option in patients who still experience the stable period without clinical indications of dialysis.Chinese Medicine (CM) is recognized as an alternative therapy on alleviating uremic symptoms, deferring dialysis initiation, and improving quality of life. Although the effects of CM on kidney disease have been demonstrated in animal experiments, evidence from large clinical trial is insufficient. So we raise the hypothesis that CM therapies including Chinese herbal formula, Chinese patent medicine via oral pattern and/or Colonic administration, will defer the initiation of dialysis in adults with stage 5 CKD.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 875
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

Related Conditions & MeSH terms

• End-Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• CM 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
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.

Locations

Country	Name	City	State
China	China PLA General Hospital	Beijing	Beijing
China	China-Japan Friendship Hospital	Beijing	Beijing
China	Dongzhimen Hospital of Beijing University of Chinese Medicine	Beijing	Beijing
China	First Hospital of Peking University	Beijing	Beijing
China	Guang'anmen Hospital China Academy of traditional Chinese Medicine	Beijing	Beijing
China	Xiyuan Hospital, Academy of traditional Chinese Medicine	Beijing	Beijing
China	Affiliated Hospital of Chengdu University of Traditional Chinese Medicine	Chengdu	Sichuan
China	Third Military Medical University Xinqiao Hospital	Chongqing	Chongqing
China	General hospital of Guangzhou Military command of PLA	Guangzhou	Guangdong
China	Guangdong Provincial Hospital of Chinese Medicine	Guangzhou	Guangdong
China	Guangzhou No.1 People's Hospital	Guangzhou	Guangdong
China	Huadu District People's Hospital of Guangzhou	Guangzhou	Guangdong
China	TCM Integrated Hospital of Southern Medical University	Guangzhou	Guangdong
China	First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine	Guiyang	Guizhou
China	First Affiliated Hospital of Heilongjiang University Of Chinese Medicine	Ha'erbin	Heilongjiang
China	Heilongjiang Academy of Traditional Chinese Medicine	Ha'erbin	Heilongjiang
China	Hangzhou Hospital of Chinese Medicine	Hangzhou	Zhejiang
China	Tong De Hospital, Zhejiang Province	Hangzhou	Zhejiang
China	Anhui Provincial Hospital of Chinese Medicine	Hefei	Anhui
China	Liuzhou Hospital of traditional Chinese Medicine	Liuzhou	Guangxi
China	Jiangsu Provincial Hospital of Chinese Medicine	Nanjing	Jiangsu
China	First Affiliated Hospital of Guangxi University Of Chinese Medicine	Nanning	Guangxi
China	Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine	Shanghai	Shanghai
China	The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University	Shanghai	Shanghai
China	First hospital of Shanxi Medical University	Taiyuan	Shanxi
China	First Affiliated Hospital of Tianjin University Of Chinese Medicine	Tianjin	Tianjin
China	Hubei Provincial Hospital of Chinese Medicine	Wuhan	Hubei
China	Shaanxi Provincial Hospital of Chinese Medicine	Xi'an	Shaanxi
China	Xijing Hospital of The Fourth Military Medical University	Xi'an	Shaanxi

Sponsors (2)

Lead Sponsor	Collaborator
Guangdong Provincial Hospital of Traditional Chinese Medicine	Ministry of Science and Technology of the People´s Republic of China

Country where clinical trial is conducted

China, 

References & Publications (16)

Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China. Beijing: People's Medicial Publishing House; 2010

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. — View Citation

Emmanuel AV, Krogh K, Bazzocchi G, Leroi AM, Bremers A, Leder D, van Kuppevelt D, Mosiello G, Vogel M, Perrouin-Verbe B, Coggrave M, Christensen P; Members of working group on Trans Anal Irrigation from UK, Denmark, Italy, Germany, France and Netherlands. Consensus review of best practice of transanal irrigation in adults. Spinal Cord. 2013 Oct;51(10):732-8. doi: 10.1038/sc.2013.86. Epub 2013 Aug 20. — View Citation

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. — View Citation

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney inter., Suppl.2013;3: 1-150.

Li Z, Zhu L, Zhang H, Yang J, Zhao J, Du D, Meng J, Yang F, Zhao Y, Sun J. Protective effect of a polysaccharide from stem of Codonopsis pilosula against renal ischemia/reperfusion injury in rats. Carbohydr Polym. 2012 Nov 6;90(4):1739-43. doi: 10.1016/j.carbpol.2012.07.062. Epub 2012 Jul 31. — View Citation

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. — View Citation

Rosansky S, Glassock RJ, Clark WF. Early start of dialysis: a critical review. Clin J Am Soc Nephrol. 2011 May;6(5):1222-8. doi: 10.2215/CJN.09301010. Review. — View Citation

Rosansky SJ, Clark WF, Eggers P, Glassock RJ. Initiation of dialysis at higher GFRs: is the apparent rising tide of early dialysis harmful or helpful? Kidney Int. 2009 Aug;76(3):257-61. doi: 10.1038/ki.2009.161. Epub 2009 May 20. Review. — View Citation

Rosansky SJ, Eggers P, Jackson K, Glassock R, Clark WF. Early start of hemodialysis may be harmful. Arch Intern Med. 2011 Mar 14;171(5):396-403. doi: 10.1001/archinternmed.2010.415. Epub 2010 Nov 8. — View Citation

Song J, Meng L, Li S, Qu L, Li X. A combination of Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis, improved renal microvascular insufficiency in 5/6 nephrectomized rats. Vascul Pharmacol. 2009 May-Jun;50(5-6):185-93. doi: 10.1016/j.vph.2009.01.005. — View Citation

Tattersall J, Dekker F, Heimbürger O, Jager KJ, Lameire N, Lindley E, Van Biesen W, Vanholder R, Zoccali C; ERBP Advisory Board. When to start dialysis: updated guidance following publication of the Initiating Dialysis Early and Late (IDEAL) study. Nephrol Dial Transplant. 2011 Jul;26(7):2082-6. doi: 10.1093/ndt/gfr168. Epub 2011 May 5. — View Citation

Tong Y, Han B, Guo H, Liu Y. Protection of Chinese herbs against adenine-induced chronic renal failure in rats. Afr J Tradit Complement Altern Med. 2010;7(4):331-8. Epub 2010 Jul 3. — View Citation

Wang YJ, He LQ, Sun W, Lu Y, Wang XQ, Zhang PQ, Wei LB, Cao SL, Yang NZ, Ma HZ, Gao J, Li P, Tao XJ, Yuan FH, Li J, Yao C, Liu X. Optimized project of traditional Chinese medicine in treating chronic kidney disease stage 3: a multicenter double-blinded randomized controlled trial. J Ethnopharmacol. 2012 Feb 15;139(3):757-64. doi: 10.1016/j.jep.2011.12.009. Epub 2011 Dec 13. — View Citation

Wright S, Klausner D, Baird B, Williams ME, Steinman T, Tang H, Ragasa R, Goldfarb-Rumyantzev AS. Timing of dialysis initiation and survival in ESRD. Clin J Am Soc Nephrol. 2010 Oct;5(10):1828-35. doi: 10.2215/CJN.06230909. Epub 2010 Jul 15. — View Citation

Zou C, Lu ZY, Wu YC, Yang LH, Su GB, Jie XN, Liu XS. Colon may provide new therapeutic targets for treatment of chronic kidney disease with Chinese medicine. Chin J Integr Med. 2013 Feb;19(2):86-91. doi: 10.1007/s11655-013-1351-8. Epub 2013 Jan 31. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Liver function	aspartate aminotransferase (AST),alanine aminotransferase (ALT)	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.
Other	Complete blood count	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.
Other	Routine stool test + occult blood	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.
Other	Electrocardiogram	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.
Other	Adverse event/reaction	number of cases of any recorded adverse event/reaction per year.	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.
Primary	Time to initiation of dialysis from enrollment.	Averaged time from enrollment to dialysis initiation or death from any cause, whichever comes first.; Patients commence dialysis based on the following criteria: 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.; 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.	From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.
Secondary	all-cause mortality	percentage of subjects who die from any cause during follow-up.	From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.
Secondary	Cardio-cerebro vascular events	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.	From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.
Secondary	Hospitalization or death caused by severe infection.	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.	From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.
Secondary	incidence of severe adverse event/reaction	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.	From enrollment to dialysis initiation or death.The duration of follow up will be for a maximum of 4 years.
Secondary	Slope of reciprocal serum creatinine	Reciprocal serum creatinine (1/SCr) slope,the serum creatinine was assessed every 2 months.	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.
Secondary	Nutrition and microinflammation status	Malnutrition Inflammation Score is used to assess 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.