Trial of Pirfenidone to Prevent Progression in Chronic Kidney Disease

NCT ID: NCT04258397

Last Updated: 2022-04-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-26

Study Completion Date

2024-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chronic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Pirfenidone

Intervention Type DRUG

Pirfenidone vs. matching placebo

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.

Group Type PLACEBO_COMPARATOR

matching placebo

Intervention Type DRUG

matching placebo

Interventions

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Pirfenidone

Pirfenidone vs. matching placebo

Intervention Type DRUG

matching placebo

matching placebo

Intervention Type DRUG

Other Intervention Names

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ESBRIET ESBRIET

Eligibility Criteria

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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.
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

San Diego Veterans Healthcare System

FED

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Veterans Medical Research Foundation

OTHER

Sponsor Role lead

Responsible Party

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Joachim H. Ix

Professor of Medicine; Chief, Division of Nephrology-Hypertension, UCSD; Attending Physician VASDHS

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Joachim H Ix, MD,MAS

Role: PRINCIPAL_INVESTIGATOR

Veterans Medical Research Foundation at VASDHS

Locations

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VA San Diego Healthcare System

San Diego, California, United States

Site Status RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Joachim H Ix, MD,MAS

Role: CONTACT

858-552-8585 ext. 7528

Erick O Castro, BS

Role: CONTACT

858-552-8585 ext. 1426

Facility Contacts

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Erick O Castro, BS

Role: primary

858-642-1426

Lidia J Espino

Role: primary

415-502-5108

Juan Espinoza

Role: backup

415-502-1886

References

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Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012 Jan 14;379(9811):165-80. doi: 10.1016/S0140-6736(11)60178-5. Epub 2011 Aug 15.

Reference Type BACKGROUND
PMID: 21840587 (View on PubMed)

Fried LF, Biggs ML, Shlipak MG, Seliger S, Kestenbaum B, Stehman-Breen C, Sarnak M, Siscovick D, Harris T, Cauley J, Newman AB, Robbins J. Association of kidney function with incident hip fracture in older adults. J Am Soc Nephrol. 2007 Jan;18(1):282-6. doi: 10.1681/ASN.2006050546. Epub 2006 Dec 13.

Reference Type BACKGROUND
PMID: 17167115 (View on PubMed)

Shlipak MG, Stehman-Breen C, Fried LF, Song X, Siscovick D, Fried LP, Psaty BM, Newman AB. The presence of frailty in elderly persons with chronic renal insufficiency. Am J Kidney Dis. 2004 May;43(5):861-7. doi: 10.1053/j.ajkd.2003.12.049.

Reference Type BACKGROUND
PMID: 15112177 (View on PubMed)

Kurella M, Chertow GM, Fried LF, Cummings SR, Harris T, Simonsick E, Satterfield S, Ayonayon H, Yaffe K. Chronic kidney disease and cognitive impairment in the elderly: the health, aging, and body composition study. J Am Soc Nephrol. 2005 Jul;16(7):2127-33. doi: 10.1681/ASN.2005010005. Epub 2005 May 11.

Reference Type BACKGROUND
PMID: 15888561 (View on PubMed)

Molsted S, Prescott L, Heaf J, Eidemak I. Assessment and clinical aspects of health-related quality of life in dialysis patients and patients with chronic kidney disease. Nephron Clin Pract. 2007;106(1):c24-33. doi: 10.1159/000101481.

Reference Type BACKGROUND
PMID: 17409766 (View on PubMed)

Odden MC, Whooley MA, Shlipak MG. Depression, stress, and quality of life in persons with chronic kidney disease: the Heart and Soul Study. Nephron Clin Pract. 2006;103(1):c1-7. doi: 10.1159/000090112. Epub 2005 Dec 7.

Reference Type BACKGROUND
PMID: 16340237 (View on PubMed)

Hailpern SM, Melamed ML, Cohen HW, Hostetter TH. Moderate chronic kidney disease and cognitive function in adults 20 to 59 years of age: Third National Health and Nutrition Examination Survey (NHANES III). J Am Soc Nephrol. 2007 Jul;18(7):2205-13. doi: 10.1681/ASN.2006101165. Epub 2007 Jun 6.

Reference Type BACKGROUND
PMID: 17554148 (View on PubMed)

King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. doi: 10.1056/NEJMoa1402582. Epub 2014 May 18.

Reference Type BACKGROUND
PMID: 24836312 (View on PubMed)

Cho ME, Kopp JB. Pirfenidone: an anti-fibrotic therapy for progressive kidney disease. Expert Opin Investig Drugs. 2010 Feb;19(2):275-83. doi: 10.1517/13543780903501539.

Reference Type BACKGROUND
PMID: 20050822 (View on PubMed)

Sharma K, Ix JH, Mathew AV, Cho M, Pflueger A, Dunn SR, Francos B, Sharma S, Falkner B, McGowan TA, Donohue M, Ramachandrarao S, Xu R, Fervenza FC, Kopp JB. Pirfenidone for diabetic nephropathy. J Am Soc Nephrol. 2011 Jun;22(6):1144-51. doi: 10.1681/ASN.2010101049. Epub 2011 Apr 21.

Reference Type BACKGROUND
PMID: 21511828 (View on PubMed)

Cho ME, Smith DC, Branton MH, Penzak SR, Kopp JB. Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007 Sep;2(5):906-13. doi: 10.2215/CJN.01050207. Epub 2007 Aug 16.

Reference Type BACKGROUND
PMID: 17702727 (View on PubMed)

Kline JA, Jimenez D, Courtney DM, Ianus J, Cao L, Lensing AW, Prins MH, Wells PS. Comparison of Four Bleeding Risk Scores to Identify Rivaroxaban-treated Patients With Venous Thromboembolism at Low Risk for Major Bleeding. Acad Emerg Med. 2016 Feb;23(2):144-50. doi: 10.1111/acem.12865. Epub 2016 Jan 14.

Reference Type BACKGROUND
PMID: 26765080 (View on PubMed)

Ix JH, Isakova T, Larive B, Raphael KL, Raj DS, Cheung AK, Sprague SM, Fried LF, Gassman JJ, Middleton JP, Flessner MF, Block GA, Wolf M. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J Am Soc Nephrol. 2019 Jun;30(6):1096-1108. doi: 10.1681/ASN.2018101058. Epub 2019 May 13.

Reference Type BACKGROUND
PMID: 31085679 (View on PubMed)

Malhotra R, Craven T, Ambrosius WT, Killeen AA, Haley WE, Cheung AK, Chonchol M, Sarnak M, Parikh CR, Shlipak MG, Ix JH; SPRINT Research Group. Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT. Am J Kidney Dis. 2019 Jan;73(1):21-30. doi: 10.1053/j.ajkd.2018.07.015. Epub 2018 Oct 2.

Reference Type BACKGROUND
PMID: 30291012 (View on PubMed)

Ix JH, Biggs ML, Mukamal K, Djousse L, Siscovick D, Tracy R, Katz R, Delaney JA, Chaves P, Rifkin DE, Hughes-Austin JM, Garimella PS, Sarnak MJ, Shlipak MG, Kizer JR. Urine Collagen Fragments and CKD Progression-The Cardiovascular Health Study. J Am Soc Nephrol. 2015 Oct;26(10):2494-503. doi: 10.1681/ASN.2014070696. Epub 2015 Feb 5.

Reference Type BACKGROUND
PMID: 25655067 (View on PubMed)

Zhang WR, Craven TE, Malhotra R, Cheung AK, Chonchol M, Drawz P, Sarnak MJ, Parikh CR, Shlipak MG, Ix JH; SPRINT Research Group. Kidney Damage Biomarkers and Incident Chronic Kidney Disease During Blood Pressure Reduction: A Case-Control Study. Ann Intern Med. 2018 Nov 6;169(9):610-618. doi: 10.7326/M18-1037. Epub 2018 Oct 23.

Reference Type BACKGROUND
PMID: 30357395 (View on PubMed)

Kahan BC, Morris TP. Analysis of multicentre trials with continuous outcomes: when and how should we account for centre effects? Stat Med. 2013 Mar 30;32(7):1136-49. doi: 10.1002/sim.5667. Epub 2012 Oct 30.

Reference Type BACKGROUND
PMID: 23112128 (View on PubMed)

Other Identifiers

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U01DK111510

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H200014

Identifier Type: -

Identifier Source: org_study_id

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