Clinical trial NCT04045171: Population Pharmacokinetics of Tacrolimus in Nephrotic Syndrome
Official title: Population Pharmacokinetics of Tacrolimus for Optimal Dose in Patients With Nephrotic Syndrome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Nephrotic Syndrome
Tacrolimus
Pharmacokinetics
Keywords: Nephrotic Syndrome
Tacrolimus
Population Pharmacokinetics
Lead sponsor: The Third Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Hunan Provincial People's Hospital
name: ZhuZhou Central Hospital
name: First People's Hospital of Chenzhou
First posted: 2019-08-05
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Nephrotic Syndrome are suit for use of Tacrolimus.

Brief summary: 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.


Eligibility criteria: 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。

Primary outcomes:
measure: change of plasma concentration of Tacrolimus
timeFrame: at 0hour，2hours，4hours，6hours，9hours，12hours after oral administration
Secondary outcomes:
measure: Genotypes as measured by next generation sequencing
timeFrame: one week
Other outcomes:
Locations:
Study officials:
affiliation: The Third Xiangya Hospital of Central South University
name: ZHIJUN HUANG, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.