Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy (IMN)

NCT03549663 | Unknown DMC

• 1 other identifier: XH-18-006
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The trial is a random, open, control and monocentric trial. Mainly to assess the urine protein remission rate of tacrolimus (TAC) monotherapy for idiopathic membranous nephropathy (IMN). Assuming that the urine protein remission rate of 48-week TAC for monotherapy of IMN is not lower than that in treatment group of TAC combined with glucocorticoid, attempt on de-hormonal therapy in the future IMN therapy can be attempted on the basis of the trial results.

Conditions

Idiopathic Membranous Nephropathy

Outcome Measures

Primary Outcomes (1)

• Complete remission rate of 24-hour urine protein

  The proportion of patients with complete remission of 24-hour urine protein in the total evaluated patients. Evaluation criteria of complete remission: post-therapy urine protein level is \<0.3g/24h.

  At week 48

Secondary Outcomes (3)

• Partial remission remission rate of 24-hour urine protein

  At week 48

• PLA2R antibody negative conversion rate

  At week 48

• Number of patients with adverse events

  up to 48 weeks

Study Arms (2)

Tacrolimus monotherapy

EXPERIMENTAL

Drug: Tacrolimus

Tacrolimus combined with hormone therapy

ACTIVE COMPARATOR

Drug: Tacrolimus; Drug: Prednisone

Interventions

Tacrolimus DRUG

Tacrolimus capsules: 0.5mg/pill, 50 pills/box, AstellasPharma (China) Co., Ltd.; Tacrolimus capsules: 1mg/pill, 50 pills/box, Hangzhou ZhongmeiHuadong Pharmacy Co., Ltd. Start to administer on the randomized grouping day (D0) with an initial dose by weight: initial dose of 0.05-0.075mg/kg/d (bid) following a strict administration interval of 12 hours or fasting or 2 hours after meal. Adjust TAC dose according to 24-hour urine protein, plasma concentration and eGFR changes. It is recommended that plasma trough concentration should be remained at 5-8ng/ml and TAC dose during the whole therapy stage should not be lower than 0.5mg/d. Drugs should be stopped if the 6-month therapy is ineffective. After 6-month therapy, for those whose urine protein achieved complete remission (CR) or partial remission (PR), TAC dose should be reduced gradually with a total therapy duration of 48 weeks.

Tacrolimus combined with hormone therapy; Tacrolimus monotherapy

Prednisone DRUG

Glucocorticoid (prednisone): 5mg/pill, 100 pills/bottle: Shanghai Sine Pharmaceutical Factory Co., Ltd. The initial dose of prednisone should be 0.5mg/kg/d orally (maximum dose of 40mg/d) and administration should be continued for 8-12 weeks; then reduced by the monthly decreased amount of 0.1mg/kg/d till to 0.2mg/kg/d (5-10mg) to maintain. Prednisone should be stopped after administration for the entire 48 weeks.

Also known as: Glucocorticoid

Tacrolimus combined with hormone therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 - 80 years;
• Those whose clinical manifestation and renal biopsy pathologic diagnosis are IMN (Stages I-IV) with secondary membranous nephropathy excluded;
• Those who meet any of the following high-risk IMN standards:
• Urinary protein\>8g/24h
• Serum albumin\<25g/l
• Serum PLA2R levels are 5 times higher than normal
• eGFR decline rate after confirmed IMN within 6-12 months is ≥30%
• Patients with serious complications: pulmonary embolism, lower extremity static Vein thrombosis/embolism, acute renal injury, etc.
• Those without reaching the above high-risk IMN standard, but their course of disease is \>6 months without spontaneous remission,and still present nephrotic syndrome;
• Patients who have signed the informed consent forms.

You may not qualify if:

• Those whose kidney pathological manifestation of interstitial fibrosis is \>30%;
• Those who are positive in active Hepatitis B (including HBsAg, HBeAg and HBcAb or HBsAg, HBeAb and HBC) or serological indexes (HBsAg or/and HBeAg or/and HBcAb) or infected with Hepatitis C, tuberculosis, cytomegalovirus, severe fungal or HIV infection;
• Those who suffer from untreated active digestive tract ulcer within 3 months before random grouping;
• Those who suffer from uncured malignant tumor for less than 5 years
• Those who received glucocorticoid (prednisone or prednisolone), mycophenolatemofetil, tacrolimus, cyclosporine A and other drugs for treatment within 3 months before screen with a course of treatment exceeding 4 weeks or those who received cyclophosphamide (accumulated dose\>1.0g);
• Those whose ALT, AST or total bilirubin content goes beyond 1.5 times above normal upper limit;
• Those who suffer from combined critical complications such as serious infection or other severe organ disease or dysfunction;
• Pregnant or lactating women;
• Those who are known to be allergic to drugs under trial or relevant products;
• The patients who cannot comply with the research proposal as determined by the supervising physician.
• Exit criteria
• Those with incomplete or partial relieved proteinuria for 6 months after treatment;
• Patients or their legal guardians voluntarily requests to withdraw;
• Those who need to take medications prohibited by the trail;
• Those with poor compliance or stopping the drug for over 2 weeks;

Sponsors & Collaborators

• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Shanghai Xinhua Hospital affliated to Shanghai Jiao Tong University, School of Medicine

Shanghai, Shanghai Municipality, 200092, China

RECRUITING

Related Publications (14)

• Zhu P, Zhou FD, Wang SX, Zhao MH, Wang HY. Increasing frequency of idiopathic membranous nephropathy in primary glomerular disease: a 10-year renal biopsy study from a single Chinese nephrology centre. Nephrology (Carlton). 2015 Aug;20(8):560-6. doi: 10.1111/nep.12542.

  PMID: 26086701 BACKGROUND

• Xu X, Wang G, Chen N, Lu T, Nie S, Xu G, Zhang P, Luo Y, Wang Y, Wang X, Schwartz J, Geng J, Hou FF. Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in China. J Am Soc Nephrol. 2016 Dec;27(12):3739-3746. doi: 10.1681/ASN.2016010093. Epub 2016 Jun 30.

  PMID: 27365535 BACKGROUND

• Hofstra JM, Fervenza FC, Wetzels JF. Treatment of idiopathic membranous nephropathy. Nat Rev Nephrol. 2013 Aug;9(8):443-58. doi: 10.1038/nrneph.2013.125. Epub 2013 Jul 2.

  PMID: 23820815 BACKGROUND

• du Buf-Vereijken PW, Branten AJ, Wetzels JF. Idiopathic membranous nephropathy: outline and rationale of a treatment strategy. Am J Kidney Dis. 2005 Dec;46(6):1012-29. doi: 10.1053/j.ajkd.2005.08.020.

  PMID: 16310567 BACKGROUND

• KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int 2012, 2: 139-274.

  BACKGROUND

• Ponticelli C, Zucchelli P, Passerini P, Cesana B, Locatelli F, Pasquali S, Sasdelli M, Redaelli B, Grassi C, Pozzi C, et al. A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy. Kidney Int. 1995 Nov;48(5):1600-4. doi: 10.1038/ki.1995.453.

  PMID: 8544420 BACKGROUND

• Ponticelli C, Altieri P, Scolari F, Passerini P, Roccatello D, Cesana B, Melis P, Valzorio B, Sasdelli M, Pasquali S, Pozzi C, Piccoli G, Lupo A, Segagni S, Antonucci F, Dugo M, Minari M, Scalia A, Pedrini L, Pisano G, Grassi C, Farina M, Bellazzi R. A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy. J Am Soc Nephrol. 1998 Mar;9(3):444-50. doi: 10.1681/ASN.V93444.

  PMID: 9513907 BACKGROUND

• Ramachandran R, Hn HK, Kumar V, Nada R, Yadav AK, Goyal A, Kumar V, Rathi M, Jha V, Gupta KL, Sakhuja V, Kohli HS. Tacrolimus combined with corticosteroids versus Modified Ponticelli regimen in treatment of idiopathic membranous nephropathy: Randomized control trial. Nephrology (Carlton). 2016 Feb;21(2):139-46. doi: 10.1111/nep.12569.

  PMID: 26205759 BACKGROUND

• Xu J, Zhang W, Xu Y, Shen P, Ren H, Wang W, Li X, Pan X, Chen N. Tacrolimus combined with corticosteroids in idiopathic membranous nephropathy: a randomized, prospective, controlled trial. Contrib Nephrol. 2013;181:152-62. doi: 10.1159/000348475. Epub 2013 May 8.

  PMID: 23689577 BACKGROUND

• Chen M, Li H, Li XY, Lu FM, Ni ZH, Xu FF, Li XW, Chen JH, Wang HY; Chinese Nephropathy Membranous Study Group. Tacrolimus combined with corticosteroids in treatment of nephrotic idiopathic membranous nephropathy: a multicenter randomized controlled trial. Am J Med Sci. 2010 Mar;339(3):233-8. doi: 10.1097/MAJ.0b013e3181ca3a7d.

  PMID: 20220333 BACKGROUND

• Zhu LB, Liu LL, Yao L, Wang LN. Efficacy and Safety of Tacrolimus Versus Cyclophosphamide for Primary Membranous Nephropathy: A Meta-Analysis. Drugs. 2017 Feb;77(2):187-199. doi: 10.1007/s40265-016-0683-z.

  PMID: 28084563 BACKGROUND

• Praga M, Barrio V, Juarez GF, Luno J; Grupo Espanol de Estudio de la Nefropatia Membranosa. Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial. Kidney Int. 2007 May;71(9):924-30. doi: 10.1038/sj.ki.5002215. Epub 2007 Mar 21.

  PMID: 17377504 BACKGROUND

• Liang Q, Li H, Xie X, Qu F, Li X, Chen J. The efficacy and safety of tacrolimus monotherapy in adult-onset nephrotic syndrome caused by idiopathic membranous nephropathy. Ren Fail. 2017 Nov;39(1):512-518. doi: 10.1080/0886022X.2017.1325371.

  PMID: 28562168 BACKGROUND

• Hoxha E, Thiele I, Zahner G, Panzer U, Harendza S, Stahl RA. Phospholipase A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy. J Am Soc Nephrol. 2014 Jun;25(6):1357-66. doi: 10.1681/ASN.2013040430. Epub 2014 Mar 7.

  PMID: 24610926 BACKGROUND

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

Tacrolimus; Prednisone; Glucocorticoids

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Fujun Lin, MD,PhD

  Shanghai Xinhua Hospital affiliated to Shanghai Jiao Tong University, School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fujun Lin, MD,PhD

CONTACT

+86-13917983703; linfujun@xinhuamed.com.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: June 8, 2018
• Study Start: July 4, 2018
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2021
• Last Updated: April 3, 2019

Record last verified: 2019-04

Locations

CN (1)