Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial
Introduction Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease (ESRD) in the USA and worldwide. Recent experimental and clinical data suggest that the non-specific phosphodiesterase inhibitor pentoxifylline (PTX) may decrease progression of chronic kidney disease. H...
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BMJ Publishing Group
2021-08-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/11/8/e053019.full |
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| author | Rajiv Agarwal Ian Craig Domenic J Reda Grant D Huang Kimberly Carlson David J Leehey Christina Clise Todd A Conner James S Kaufman Robert J Anderson Douglas Lammie Jeffrey Huminik Linda Polzin Conor McBurney Nicholas V Emanuele |
| author_facet | Rajiv Agarwal Ian Craig Domenic J Reda Grant D Huang Kimberly Carlson David J Leehey Christina Clise Todd A Conner James S Kaufman Robert J Anderson Douglas Lammie Jeffrey Huminik Linda Polzin Conor McBurney Nicholas V Emanuele |
| author_sort | Rajiv Agarwal |
| collection | DOAJ |
| description | Introduction Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease (ESRD) in the USA and worldwide. Recent experimental and clinical data suggest that the non-specific phosphodiesterase inhibitor pentoxifylline (PTX) may decrease progression of chronic kidney disease. However, a large-scale randomised clinical trial is needed to determine whether PTX can reduce ESRD and death in DKD.Methods and analysis Veterans Affairs (VA) PTXRx is a pragmatic, randomised, placebo-controlled multicentre VA Cooperative Study to test the hypothesis that PTX, when added to usual care, leads to a reduction in the time to ESRD or death in patients with type 2 diabetes with DKD when compared with usual care plus placebo. The study aims to enrol 2510 patients over a 4-year period with an additional up to 5-year follow-up to generate a total of 646 primary events. The primary objective of this study is to compare the time until ESRD or death (all-cause mortality) between participants randomised to PTX or placebo. Secondary endpoints will be: (1) health-related quality of life, (2) time to doubling of serum creatinine, (3) incidence of hospitalisations for congestive heart failure, (4) incidence of a three-point major adverse cardiovascular events composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), (5) incidence of peripheral vascular disease, (6) change in urinary albumin-to-creatinine ratio from baseline to 6 months and (7) rate of annual change in estimated glomerular filtration rate (eGFR) during the study period.Ethics and dissemination This study was approved by the VA Central Institutional Review Board (cIRB/18-36) and will be conducted in compliance with the Declaration of Helsinki and the Guidelines for Good Clinical Practice. The Hines Cooperative Studies Programme will finalise the study results, which will be published in accordance with the Consolidated Standards of Reporting Trials statement in a peer-reviewed scientific journal.Trial registration number NCT03625648. |
| format | Article |
| id | doaj-art-3642d0a047034902b7cdba9ffde7db80 |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2021-08-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-3642d0a047034902b7cdba9ffde7db802025-08-20T02:20:40ZengBMJ Publishing GroupBMJ Open2044-60552021-08-0111810.1136/bmjopen-2021-053019Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trialRajiv Agarwal0Ian Craig1Domenic J Reda2Grant D Huang3Kimberly Carlson4David J Leehey5Christina Clise6Todd A Conner7James S Kaufman8Robert J Anderson9Douglas Lammie10Jeffrey Huminik11Linda Polzin12Conor McBurney13Nicholas V Emanuele14Veterans’ Affairs Medical Center, Indianapolis, Indiana, USADivision of Strategic Innovation, Evaluation, and Communication, Center for Clinical Standards and Quality, Baltimore, Maryland, USACooperative Studies Program, Edward Hines Junior VA Hospital, Hines, Illinois, USAVeterans Affairs Office of Research and Development, Washington, District of Columbia, USACooperative Studies Program, Edward Hines Junior VA Hospital, Hines, Illinois, USALoyola University Medical Center, Maywood, Illinois, USAVA Cooperative Studies Program, Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico, USAVA Cooperative Studies Program, Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico, USAResearch Service, New York Harbor Health Care System, New York, New York, USAVeterans Affairs Medical Center, Omaha, Nebraska, USACooperative Studies Program, Edward Hines Junior VA Hospital, Hines, Illinois, USAVA Cooperative Studies Program, Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico, USAEdward Hines Junior VA Hospital, Hines, Illinois, USAEdward Hines Junior VA Hospital, Hines, Illinois, USAEdward Hines Junior VA Hospital, Hines, Illinois, USAIntroduction Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease (ESRD) in the USA and worldwide. Recent experimental and clinical data suggest that the non-specific phosphodiesterase inhibitor pentoxifylline (PTX) may decrease progression of chronic kidney disease. However, a large-scale randomised clinical trial is needed to determine whether PTX can reduce ESRD and death in DKD.Methods and analysis Veterans Affairs (VA) PTXRx is a pragmatic, randomised, placebo-controlled multicentre VA Cooperative Study to test the hypothesis that PTX, when added to usual care, leads to a reduction in the time to ESRD or death in patients with type 2 diabetes with DKD when compared with usual care plus placebo. The study aims to enrol 2510 patients over a 4-year period with an additional up to 5-year follow-up to generate a total of 646 primary events. The primary objective of this study is to compare the time until ESRD or death (all-cause mortality) between participants randomised to PTX or placebo. Secondary endpoints will be: (1) health-related quality of life, (2) time to doubling of serum creatinine, (3) incidence of hospitalisations for congestive heart failure, (4) incidence of a three-point major adverse cardiovascular events composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), (5) incidence of peripheral vascular disease, (6) change in urinary albumin-to-creatinine ratio from baseline to 6 months and (7) rate of annual change in estimated glomerular filtration rate (eGFR) during the study period.Ethics and dissemination This study was approved by the VA Central Institutional Review Board (cIRB/18-36) and will be conducted in compliance with the Declaration of Helsinki and the Guidelines for Good Clinical Practice. The Hines Cooperative Studies Programme will finalise the study results, which will be published in accordance with the Consolidated Standards of Reporting Trials statement in a peer-reviewed scientific journal.Trial registration number NCT03625648.https://bmjopen.bmj.com/content/11/8/e053019.full |
| spellingShingle | Rajiv Agarwal Ian Craig Domenic J Reda Grant D Huang Kimberly Carlson David J Leehey Christina Clise Todd A Conner James S Kaufman Robert J Anderson Douglas Lammie Jeffrey Huminik Linda Polzin Conor McBurney Nicholas V Emanuele Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial BMJ Open |
| title | Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial |
| title_full | Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial |
| title_fullStr | Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial |
| title_full_unstemmed | Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial |
| title_short | Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial |
| title_sort | pentoxifylline in diabetic kidney disease va ptxrx protocol for a pragmatic randomised controlled trial |
| url | https://bmjopen.bmj.com/content/11/8/e053019.full |
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