Population Pharmacokinetics of Tacrolimus in Nephrotic Syndrome (PISTONS)

Population Pharmacokinetics of Tacrolimus for Optimal Dose in Patients With Nephrotic Syndrome

This study will use a multi-center, prospective design, with a "Real World Study" model, to include 200 patients with nephrotic syndrome. based on the Population Pharmacokinetics (PPK) model, it will study genotype and clinical factors in patients with nephrotic syndrome, to explore the Pharmacokinetics/ Pharmacodynamics (PK/PD) relationship of Tacrolimus in patients with nephrotic syndrome, and develop an optimal medication regimen.

Study Overview

• Status: Unknown
• Conditions: Pharmacokinetics; Nephrotic Syndrome; Tacrolimus
• Intervention / Treatment: Drug: Tacrolimus

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Nephrotic Syndrome are suit for use of Tacrolimus.

Description

Inclusion Criteria:

• （1）Patients with Nephrotic Syndrome：

  1. Proteinuria greater than 3.5 g/24 hour
  2. Serum albumin <30 g/l
  3. Clinical evidence of peripheral oedema
  4. Hyperlipidemia 1) and 2) are necessary for diagnosis.
• （2）18-75years old（include 75），gender is not limited；
• （3）Voluntary signing informed consent。

Exclusion Criteria:

• （1）Secondary nephrotic syndrome；
• （2）Allergic to Tacrolimus or other unsuitable use of Tacrolimus；
• （3）With other immunosuppressive agents such as cyclosporin A, cyclophosphamide, mycophenolate mofetil, leflunomide, tripterygium wilfordii (hormone is not restricted)；
• （4）Severe liver dysfunction (transaminase > 3 ULN, or bilirubin > 3 ULN)；
• （5）Severe renal insufficiency（eGFR<30 ml/min/1.73m2）
• （6）Joined other clinical trials within 1 month；
• （7）Missing clinical data；
• （8）Pregnancy, lactation or planning for pregnancy within 12 months；
• （9）Researchers believe that patients who are not suitable for this clinical trial。

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of plasma concentration of Tacrolimus	Study the plasma concentration of Tacrolimus in patients with nephrotic syndrome	at 0hour，2hours，4hours，6hours，9hours，12hours after oral administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genotypes as measured by next generation sequencing	Genotypes as measured by next generation sequencing	one week

Collaborators and Investigators

• Sponsor: The Third Xiangya Hospital of Central South University
• Collaborators: Hunan Provincial People's Hospital; ZhuZhou Central Hospital; First People's Hospital of Chenzhou
• Investigators: Principal Investigator: ZHIJUN HUANG, Dr., The Third Xiangya Hospital of Central South University

Publications and helpful links

General Publications

• Lu T, Zhu X, Xu S, Zhao M, Huang X, Wang Z, Zhao L. Dosage Optimization Based on Population Pharmacokinetic Analysis of Tacrolimus in Chinese Patients with Nephrotic Syndrome. Pharm Res. 2019 Feb 4;36(3):45. doi: 10.1007/s11095-019-2579-6.
• Hao GX, Huang X, Zhang DF, Zheng Y, Shi HY, Li Y, Jacqz-Aigrain E, Zhao W. Population pharmacokinetics of tacrolimus in children with nephrotic syndrome. Br J Clin Pharmacol. 2018 Aug;84(8):1748-1756. doi: 10.1111/bcp.13605. Epub 2018 May 22.
• Radhakrishnan J, Cattran DC. The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. Kidney Int. 2012 Oct;82(8):840-56. doi: 10.1038/ki.2012.280. Epub 2012 Aug 15.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 10, 2019
• Primary Completion (Anticipated): July 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Actual): August 5, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Tacrolimus; Nephrotic Syndrome; Population Pharmacokinetics
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: XY3-IIT-TAC1905A01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We welcomes researchers interested in collaboration. We request a short research proposal including information on the background, research questions and methods, timetable and budget, and authorship. For more information please contact the principal investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No