Trial of Pirfenidone to Prevent Progression in Chronic Kidney Disease (TOP-CKD)

April 25, 2022 updated by: Joachim H. Ix, Veterans Medical Research Foundation

Trial of Pirfenidone to Prevent Progression in Chronic Kidney Disease (TOP-CKD)

Kidney disease is a global health problem, affecting more than 10% of the world's population and more than half of adults over 70 years of age in the United States. Persons with kidney disease are at higher risk for cardiovascular disease, heart failure, physical function decline, and mortality. Kidney scarring is a dominant factor in the development of kidney disease. Our group has evaluated several tests to determine the severity of scarring without requiring kidney biopsies, using MRI imaging scans and evaluating markers of scarring that we can measure in the urine. In this study we will use these measures to evaluate pirfenidone as a promising potential new treatment for patients with kidney disease.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The TOP-CKD clinical trial is a randomized, double-blind, placebo-controlled interventional study, phase 2 trial of pirfenidone vs. placebo in 200 persons with Chronic Kidney Disease (CKD) with an eGFR ≥ 20 ml/min/1.73 m2 and a risk of progression to End Stage Renal Disease (ESRD) of at least 1% over five years. Participants receive treatment for 12 months, followed by a 6 month off-treatment follow-up period. Kidney scarring, also known as fibrosis, is a dominant factor in the development of kidney disease. This study will evaluate several tests to determine the severity of scarring without requiring kidney biopsies, using MRI imaging scans and evaluating markers of scarring that we can measure in the urine. We will use these measures to evaluate pirfenidone as a promising potential new treatment for patients with CKD.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92161
        • Recruiting
        • VA San Diego Healthcare System
        • Contact:
          • Erick O Castro, BS
          • Phone Number: 858-642-1426
        • Principal Investigator:
          • Joachim H Ix, MD
        • Sub-Investigator:
          • Dena Rifkin, MD
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California, San Francisco
        • Contact:
          • Lidia J Espino
          • Phone Number: 415-502-5108
        • Contact:
          • Juan Espinoza
          • Phone Number: 415-502-1886
        • Principal Investigator:
          • Michael Shlipak, MD
        • Sub-Investigator:
          • Meyeon Park, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with eGFR ≥20 ml/min/1.73m2 using the CKD-EPI Creatinine equation.
  • Four variable Kidney Failure Risk Equation (KFRE) 5 year risk score >1%
  • Age 21 years or older.

Exclusion Criteria:

To be determined at the screening visit or, for laboratory data, within 3 months of the screening visit if available from clinical care.

  • Participants with known autosomal dominant polycystic kidney disease.
  • Use or planned use of drugs that inhibit CYP1A2 which may increase pirfenidone exposure ( for example, artemisin, atazanavir, cimetidine, ciprofloxacin, enoxacin, ethinyl estradiol, fluvoxamine, mexiletine, tacrine, thiabendazole, or zileuton).
  • Liver disease: clinical cirrhosis by imaging or physician diagnosis; alcohol use > 14 drinks/week; or aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin concentrations > 2 times the upper limit of normal (ULN) based on thresholds set at each site's local clinical laboratory.
  • Clinical idiopathic pulmonary fibrosis (IPF) by imaging or physician diagnosis (pirfenidone is indicated for patients with IPF).
  • Electrocardiogram (ECG) with a QTc interval > 500 msec at screening (pirfenidone can prolong QTc).
  • Family or personal history of long QT Syndrome.
  • Known hypersensitivity to pirfenidone.
  • Current use of tobacco, including cigarettes, cigars, chewing tobacco, or vaping products. (Current use is defined as any use in the past 3 months).
  • Physical inability, claustrophobia or other contra-indication to obtaining MRI measurements.
  • Current participation in another clinical trial (observational studies are exempted).
  • Systemic immunosuppressive medications (<10 mg daily prednisone or inhaled steroids are exempted).
  • Malignancy within 2 years (non-melanoma skin and localized prostate carcinoma are exempted).
  • Institutionalized individuals (e.g. prisoners, long term care residents).
  • Pregnancy, planning to become pregnant, or currently breast-feeding; women under 55 will need to either have a reliable method of birth control (IUD {intrauterine device}, oral contraceptive pills {OCPs}) or have no menses in the preceding 2 years.
  • Life expectancy < 12 months as assessed by the site investigator.
  • Plans to leave the immediate area in < 12 months.
  • Anticipated need for dialysis or kidney transplantation within 12 months.
  • Hospitalization within the past 30 days (24-hour observation admissions are exempted).
  • Active alcohol or substance abuse within the last 12 months, as assessed by the site investigator.
  • Active treatment of uncontrolled psychiatric disease, as assessed by the site investigator.
  • Perceived inability to adhere to the medical regimen or comply with recommendations, as determined by the site investigator.
  • Inability or unwillingness to travel to study visits.
  • Any condition that, in the opinion of the site investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Experimental, pirfenidone

Pirfenidone 267 mg capsules

Randomized participants will take 5 capsules (1335 mg pirfenidone): 2 pills in the morning, 1 mid-day, and 2 in the evening, with meals.
Drug: Pirfenidone
Pirfenidone vs. matching placebo
Other Names:
  • ESBRIET
Placebo Comparator: Placebo, pirfenidone

Pirfenidone placebo capsules

Randomized participants will take 5 capsules (1335 mg pirfenidone): 2 pills in the morning, 1 mid-day, and 2 in the evening, with meals.
Drug: matching placebo
matching placebo
Other Names:
  • ESBRIET

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in kidney fibrosis, as assessed by diffusion-weighted magnetic resonance imaging (DW-MRI).
Time Frame: Baseline to Month 12
The slope of change in apparent diffusion coefficient of the cortex of the kidney on the diffusion-weighted renal MRI over 12 months.
Baseline to Month 12
Change from baseline in kidney fibrosis, as assessed by urinary markers of tubulo-interstitial fibrosis.
Time Frame: Baseline to Month 12
The slope of change of urine alpha 1 microglobulin (α1M), N-terminal procollagen type 3 peptide (PIIINP), and monocyte chemoattractant protein-1 (MCP-1) over 12 months.
Baseline to Month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in kidney function, as assessed by eGFR.
Time Frame: Baseline to Month 18
Change in eGFR will be evaluated as a secondary endpoint, using linear mixed models with random intercepts and slopes. Estimates from the linear mixed models will be interpretable as annual change in slope.
Baseline to Month 18
Change from baseline in kidney function, as assessed by urine albumin to creatinine ratio (ACR).
Time Frame: Baseline to Month 18
Change in ACR will be evaluated as a secondary endpoint, using linear mixed models with random intercepts and slopes. Estimates from the linear mixed models will be interpretable as annual change in slope. Because urine concentrations of ACR are typically right-skewed, we will use a log transformation to normalize its distribution.
Baseline to Month 18

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Veterans Medical Research Foundation

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of California, San Diego
Genentech, Inc.
University of California, San Francisco
San Diego Veterans Healthcare System

Investigators

  • Principal Investigator: Joachim H Ix, MD,MAS, Veterans Medical Research Foundation at VASDHS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2020

Primary Completion (Anticipated)

May 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

February 4, 2020

First Submitted That Met QC Criteria

February 5, 2020

First Posted (Actual)

February 6, 2020

Study Record Updates

Last Update Posted (Actual)

April 27, 2022

Last Update Submitted That Met QC Criteria

April 25, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H200014
  • U01DK111510 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

The study data will be archived in the NIDDK Data Repository

IPD Sharing Time Frame

We anticipate that the data and documentation will be provided to the NIDDK Data Repository when the study is complete (2024) and will become available approximately six months later.

IPD Sharing Access Criteria

Formal request to the NIDDK Central Repository

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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