Condition category
Urological and Genital Diseases
Date applied
11/05/2016
Date assigned
28/05/2016
Last edited
26/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Idiopathic membranous nephropathy (IMN) is a disease where the small blood vessels in the kidney become inflamed and thickened, causing proteins to leak into the urine. The aims of this study are to compare the effectiveness of a steroid combined with tacrolimus and tacrolimus alone for the treatment of IMN.

Who can participate?
Patients with IMN

What does the study involve?
Patients are randomly allocated into two groups: one group receives TAC alone, and the other group receives steroid combined with TAC. Patients are followed up for 6 months.

What are the possible benefits and risks of participating?
All patients will receive TAC for free, and will help us to provide a better treatment for IMN. The risks include adverse reactions to TAC, such as high blood pressure, angina pectoris, effusion and so on.

Where is the study run from?
The First Affiliated Hospital of Zhengzhou University (China)

When is the study starting and how long is it expected to run for?
June 2016 to June 2017

Who is funding the study?
The First Affiliated Hospital of Zhengzhou University (China)

Who is the main contact?
Zhanzheng Zhao
13938525666@139.com

Trial website

Contact information

Type

Scientific

Primary contact

Mr Zhanzheng Zhao

ORCID ID

Contact details

No.1 Jianshe Eastern Road
6th Floor of No.7th Building
Erqi District
Zhengzhou
450000
China
+86 (0)139 38525666
13938525666@139.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

A randomized controlled study of tacrolimus for the treatment of idiopathic membranous nephropathy

Acronym

Study hypothesis

Membranous nephropathy (MN) is one of the most common pathological causes of nephrotic syndrome in adults. Idiopathic membranous nephropathy (IMN) accounts for approximately two-thirds of all MN cases. The clinical manifestations and prognosis vary greatly in IMN patients, and IMN may resolve without treatment, present as ongoing nephrotic syndrome, or progress to end-stage renal disease. No consensus on its treatment or widely accepted treatment protocol is currently available.

Tacrolimus (TAC), an immunosuppressant, is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp). Steroids are substrates and inducers of P-gp and CYP3A4 and potent inducers of multidrug resistance-associated protein 2 (MRP2) and UDP-glucuronosyltransferase (UGT). The plasma concentration of TAC increases after steroid withdrawal. In vivo pharmacokinetic studies in animals showed that TAC combined with prednisone decreases the plasma concentration of TAC and increases the elimination of TAC.

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend the use of TAC for at least 6 months in patients who meet the criteria for initial treatment but are unwilling or contraindicated to receive cycles of steroids/alkylating agents (1C). TAC alone or in combination with a steroid is more effective for MN than conventional treatment regimens. However, no studies have been conducted to compare the efficacy and side effects of TAC alone and TAC combined with a steroid for the treatment of MN.

We hypothesize that in combination therapy of a steroid and TAC for IMN, the steroid will reduce the plasma concentration of TAC and make it necessary to increase the TAC dose, thereby increasing the side effects of TAC.

Ethics approval

The Ethics Committee of First Affiliated Hospital of Zhengzhou University, 25/12/2015, ref: Scientific 2015(35)

Study design

Multicenter randomized controlled clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Idiopathic membranous nephropathy

Intervention

1. Treatment regimen: The patients will be randomly assigned into one of the two groups: steroid + TAC group (P + T group) or TAC alone group (T group), and observed for 24 weeks.

Patients in the P + T group will be given prednisone 0.5 mg/kg/d (maximum dose: 30 mg/d); the dose will be tapered 2 weeks after the patient has achieved clinical remission, at a rate of 5 mg/d every 2 weeks; once the dose has been reduced to 10 mg/d, the dose will be tapered at a rate of 2.5 mg/d every two weeks until withdrawal; for patients who fail to achieve clinical remission within 4 weeks, the dose will be tapered as described above.

Patients in the T group will receive TAC 0.05 mg/kg/d (two doses per day, morning and night) 1 hour before or 2 hours after meals. The TAC dose is adjusted on the basis of its plasma concentration, and the goal is to maintain the plasma concentration in the range of 5–10 ng/mL. To reduce the TAC dose, for both groups, TAC will be reduced by 30% at 2 months after complete or partial clinical remission. The plasma concentration of TAC will be maintained at 3-6 ng/mL.

2. Concomitant medications: The following medications are prohibited: other immunosuppressants or cytotoxic drugs and anticoagulants.

Intervention type

Drug

Phase

Not Applicable

Drug names

Tacrolimus

Primary outcome measures

1. Change in 24-hour urine protein from baseline and percent change
2. Change in serum albumin from baseline and percent change
Measured at baseline, 2, 4, 8, 12, 24 weeks.

Secondary outcome measures

1. Changes in serum creatinine and eGFR from baseline and percent changes
2. Change in serum PLA2R antibodies from baseline
Measured at baseline, 2, 4, 8, 12, 24 weeks.

Overall trial start date

01/06/2016

Overall trial end date

30/06/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with idiopathic membranous nephropathy confirmed by renal biopsy (light microscopy + SEM)
2. Clinical manifestations of nephrotic syndrome
3. Persistent serum creatinine < 115 mmol/L or the reference value of creatinine
4. Any age group, male or female

Participant type

Patient

Age group

All

Gender

Both

Target number of participants

120

Participant exclusion criteria

1. Secondary MN with hepatitis or malignant tumor
2. Use of steroids, cytotoxic drugs, or immunosuppressants within 3 months of this study
3. Other severe organ diseases
4. Fasting blood glucose > 6.2 mmol/L or confirmed diabetes
5. Pregnant or nursing women

Recruitment start date

01/06/2016

Recruitment end date

30/03/2017

Locations

Countries of recruitment

China

Trial participating centre

The First Affiliated Hospital of Zhengzhou University
Zhengzhou
45000
China

Trial participating centre

The First Affiliated Hospital of Henan University of Chinese Medicine
Zhengzhou
450000
China

Trial participating centre

The First Affiliated Hospital of Henan University of Science and Technology
LuoYang
471023
China

Trial participating centre

LuoHe Central Hospital
LuoHe
671699
China

Trial participating centre

ZhuMaDian Central Hospital
ZhuMaDian
463699
China

Sponsor information

Organisation

The First Affiliated Hospital of Zhengzhou University (China)

Sponsor details

No.1 Jianshe Eastern Road
6th Floor of No.7th Building
Erqi District
Zhengzhou
450000
China
+86 (0)371 66295962
13938525666@139.com

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

The First Affiliated Hospital of Zhengzhou University (China)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes