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Chronic Kidney DiseasePhase 2TOP-CKDNCT04258397

Trial of Pirfenidone to Prevent Progression in Chronic Kidney Disease

A Phase 2 study testing Pirfenidone in people with Chronic Kidney Disease, run by Veterans Medical Research Foundation at 2 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Chronic Kidney Disease
What is being tested?
Pirfenidone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
200 participants
Where
2 sitesUnited States
Study dates
26 Oct 2020to Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 24Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites, 2 recruiting
  • VA San Diego Healthcare System

    San Diego, California, 92161

    Erick O Castro, BS, 858-642-1426

    Joachim H Ix, MD

    Recruiting
  • University of California, San Francisco

    San Francisco, California, 94143

    Lidia J Espino, 415-502-5108

    Juan Espinoza, 415-502-1886

    Recruiting

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Pirfenidone, matching placebo
Keywords
Fibrosis, Scarring, CKD
Medical subject headings
Renal Insufficiency, Chronic, Fibrosis, Cicatrix

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PirfenidoneDrug

    Also called ESBRIET

    Pirfenidone vs. matching placebo

  • matching placeboDrug

    Also called ESBRIET

    matching placebo

Study groups in NCT04258397
Study groupRoleWhat they receive
Experimental, pirfenidoneActive comparatorPirfenidone 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.
Receives: Drug: Pirfenidone
Placebo, pirfenidonePlacebo comparatorPirfenidone 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.
Receives: Drug: matching placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline in kidney fibrosis, as assessed by diffusion-weighted magnetic resonance imaging (DW-MRI).

    The slope of change in apparent diffusion coefficient of the cortex of the kidney on the diffusion-weighted renal MRI over 12 months.

    Measured: Baseline to Month 12

  2. Change from baseline in kidney fibrosis, as assessed by urinary markers of tubulo-interstitial fibrosis.

    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.

    Measured: Baseline to Month 12

Secondary outcomes (2)
  1. Change from baseline in kidney function, as assessed by eGFR.

    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.

    Measured: Baseline to Month 18

  2. Change from baseline in kidney function, as assessed by urine albumin to creatinine ratio (ACR).

    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.

    Measured: Baseline to Month 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2020
  2. Study start26 Oct 2020
  3. Primary completionMay 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04258397
Sponsor's protocol ID
H200014
Other IDs
U01DK111510
Acronym
TOP-CKD
Status last verified
Apr 2022
First submitted
4 Feb 2020
Last updated
27 Apr 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The study data will be archived in the NIDDK Data Repository

Publications

  • 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.

    PubMed 21840587
  • 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.

    PubMed 17167115
  • 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.

    PubMed 15112177
  • 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.

    PubMed 15888561
  • 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.

    PubMed 17409766
  • 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.

    PubMed 16340237
  • 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.

    PubMed 17554148
  • 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.

    PubMed 24836312
  • 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.

    PubMed 20050822
  • 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.

    PubMed 21511828
  • 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.

    PubMed 17702727
  • 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.

    PubMed 26765080
  • 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.

    PubMed 31085679
  • 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.

    PubMed 30291012
  • 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.

    PubMed 25655067

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pirfenidone in people with Chronic Kidney Disease, run by Veterans Medical Research Foundation at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Joachim H Ix, MD,MAS (858-552-8585 ext. 7528, joeix@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline in kidney fibrosis, as assessed by diffusion-weighted magnetic resonance imaging (DW-MRI). (time frame: Baseline to Month 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04258397, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2022.

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