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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04258397
Recruitment Status : Recruiting
First Posted : February 6, 2020
Last Update Posted : April 27, 2022
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
San Diego Veterans Healthcare System
University of California, San Diego
University of California, San Francisco
Genentech, Inc.
Information provided by (Responsible Party):
Joachim H. Ix, Veterans Medical Research Foundation

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Drug: Pirfenidone Drug: matching placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Official Title: Trial of Pirfenidone to Prevent Progression in Chronic Kidney Disease (TOP-CKD)
Actual Study Start Date : October 26, 2020
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
Drug Information available for: Pirfenidone

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 Name: 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 Name: ESBRIET




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04258397


Contacts
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Contact: Joachim H Ix, MD,MAS 858-552-8585 ext 7528 joeix@health.ucsd.edu
Contact: Erick O Castro, BS 858-552-8585 ext 1426 erick.castro@va.gov

Locations
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United States, California
VA San Diego Healthcare System Recruiting
San Diego, California, United States, 92161
Contact: Erick O Castro, BS    858-642-1426      
Principal Investigator: Joachim H Ix, MD         
Sub-Investigator: Dena Rifkin, MD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Lidia J Espino    415-502-5108      
Contact: Juan Espinoza    415-502-1886      
Principal Investigator: Michael Shlipak, MD         
Sub-Investigator: Meyeon Park, MD         
Sponsors and Collaborators
Veterans Medical Research Foundation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
San Diego Veterans Healthcare System
University of California, San Diego
University of California, San Francisco
Genentech, Inc.
Investigators
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Principal Investigator: Joachim H Ix, MD,MAS Veterans Medical Research Foundation at VASDHS
Publications:

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Responsible Party: Joachim H. Ix, Professor of Medicine; Chief, Division of Nephrology-Hypertension, UCSD; Attending Physician VASDHS, Veterans Medical Research Foundation
ClinicalTrials.gov Identifier: NCT04258397    
Other Study ID Numbers: H200014
U01DK111510 ( U.S. NIH Grant/Contract )
First Posted: February 6, 2020    Key Record Dates
Last Update Posted: April 27, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The study data will be archived in the NIDDK Data Repository
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
Access Criteria: Formal request to the NIDDK Central Repository

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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
Keywords provided by Joachim H. Ix, Veterans Medical Research Foundation:
Fibrosis
Scarring
CKD
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Pirfenidone
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents