A Multicenter, Randomized, Controlled, Clinical Trial Evaluating a Lyopreserved Amniotic Membrane in the Treatment of Venous Leg Ulcers

ABSTRACT Background Standard of Care (SoC) with multilayer compression therapy along with proper wound management, may not be sufficient to close all venous ulcers and needs advanced therapies. Methods In this multicenter, prospective, randomized, controlled, open‐label trial, 351 patients were scre...

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Main Authors: Yadwinder Dhillon, Lena Levine, Gregory Tovmassian, Alexander Reyzelman, Francisco Perez‐Clavijo, Francis Wodie, Shawn Cazzell, Allan Grossman, Lesly Robinson, Felix Sigal, Robert S Kirsner, Mher Vartivarian, Molly Saunders, Jaideep Banerjee
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Health Science Reports
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Online Access:https://doi.org/10.1002/hsr2.70819
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author Yadwinder Dhillon
Lena Levine
Gregory Tovmassian
Alexander Reyzelman
Francisco Perez‐Clavijo
Francis Wodie
Shawn Cazzell
Allan Grossman
Lesly Robinson
Felix Sigal
Robert S Kirsner
Mher Vartivarian
Molly Saunders
Jaideep Banerjee
author_facet Yadwinder Dhillon
Lena Levine
Gregory Tovmassian
Alexander Reyzelman
Francisco Perez‐Clavijo
Francis Wodie
Shawn Cazzell
Allan Grossman
Lesly Robinson
Felix Sigal
Robert S Kirsner
Mher Vartivarian
Molly Saunders
Jaideep Banerjee
author_sort Yadwinder Dhillon
collection DOAJ
description ABSTRACT Background Standard of Care (SoC) with multilayer compression therapy along with proper wound management, may not be sufficient to close all venous ulcers and needs advanced therapies. Methods In this multicenter, prospective, randomized, controlled, open‐label trial, 351 patients were screened, 200 were eligible and enrolled and were randomized 1:1 to LPM (lyopreserved cellular placental membrane) plus SoC or SoC alone for up to 12 weeks. Patients were enrolled between June 2018 and November 2020 at 30 sites across the United States. Outcome measures included complete closure of the index ulcer (primary), reduction in wound size, rate of closure, quality of life, and adverse events. Results ITT analysis revealed that wounds treated with weekly applications of LPM as an adjunct to standard of care, reduced in size significantly more than SoC alone, at the end of 4, 8, and 12 graft applications, indicating a faster progression to closure. There was a statistically 1.72 higher relative risk or 72% higher probability of wound closure with LPM compared to the SoC group during the study period for wounds with an initial size of 3–25 cm2. Use of LPM as an adjunct was able to close statistically larger‐sized wounds on average. There was also a statistically significant fivefold improvement in quality of life (overall physical symptoms and daily life) over baseline, in the LPM treated patients as compared to the control group. Conclusion LPM and standard of care, significantly closed more venous leg ulcers and faster than standard of care alone and improved the quality of life for patients, suggesting that the use of aseptically processed LPM is a safe and effective treatment option in the healing of chronic venous leg ulcers. Trial Registration: ClinicalTrials.gov ID: NCT03629236, Study to Evaluate Safety and Efficacy of GrafixPL for the Treatment of Venous Leg Ulcers. (https://clinicaltrials.gov/study/NCT03629236).
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spelling doaj-art-1033fabfdc6f4831b141c2bc6048870a2025-08-20T03:59:36ZengWileyHealth Science Reports2398-88352025-05-0185n/an/a10.1002/hsr2.70819A Multicenter, Randomized, Controlled, Clinical Trial Evaluating a Lyopreserved Amniotic Membrane in the Treatment of Venous Leg UlcersYadwinder Dhillon0Lena Levine1Gregory Tovmassian2Alexander Reyzelman3Francisco Perez‐Clavijo4Francis Wodie5Shawn Cazzell6Allan Grossman7Lesly Robinson8Felix Sigal9Robert S Kirsner10Mher Vartivarian11Molly Saunders12Jaideep Banerjee13Titan Clinical Solutions Phoenix Arizona USAAcclaim Bone & Joint Institute Fort Worth Texas USACenter for Clinical Research Carmichael California USACenter for Clinical Research Castro Valley California USAIntegral Clinical Trials Solutions Doral Florida USAIntegral Clinical Trials Solutions Homestead Florida USALimb Preservation Platform Fresno California USAHarrisburg Foot and Ankle Center Harrisburg Pennsylvania USATemple University School of Podiatric Medicine Philadelphia Pennsylvania USALA Foot Pain and Ankle Clinic Los Angeles California USAUniversity of Miami Miami Florida USACenter for Clinical Research San Francisco California USAOsiris Therapeutics Columbia Maryland USASmith & Nephew Inc. Fortworth Texas USAABSTRACT Background Standard of Care (SoC) with multilayer compression therapy along with proper wound management, may not be sufficient to close all venous ulcers and needs advanced therapies. Methods In this multicenter, prospective, randomized, controlled, open‐label trial, 351 patients were screened, 200 were eligible and enrolled and were randomized 1:1 to LPM (lyopreserved cellular placental membrane) plus SoC or SoC alone for up to 12 weeks. Patients were enrolled between June 2018 and November 2020 at 30 sites across the United States. Outcome measures included complete closure of the index ulcer (primary), reduction in wound size, rate of closure, quality of life, and adverse events. Results ITT analysis revealed that wounds treated with weekly applications of LPM as an adjunct to standard of care, reduced in size significantly more than SoC alone, at the end of 4, 8, and 12 graft applications, indicating a faster progression to closure. There was a statistically 1.72 higher relative risk or 72% higher probability of wound closure with LPM compared to the SoC group during the study period for wounds with an initial size of 3–25 cm2. Use of LPM as an adjunct was able to close statistically larger‐sized wounds on average. There was also a statistically significant fivefold improvement in quality of life (overall physical symptoms and daily life) over baseline, in the LPM treated patients as compared to the control group. Conclusion LPM and standard of care, significantly closed more venous leg ulcers and faster than standard of care alone and improved the quality of life for patients, suggesting that the use of aseptically processed LPM is a safe and effective treatment option in the healing of chronic venous leg ulcers. Trial Registration: ClinicalTrials.gov ID: NCT03629236, Study to Evaluate Safety and Efficacy of GrafixPL for the Treatment of Venous Leg Ulcers. (https://clinicaltrials.gov/study/NCT03629236).https://doi.org/10.1002/hsr2.70819allograftsamniotic membranequality of lifeskin substitutevenous ulcers
spellingShingle Yadwinder Dhillon
Lena Levine
Gregory Tovmassian
Alexander Reyzelman
Francisco Perez‐Clavijo
Francis Wodie
Shawn Cazzell
Allan Grossman
Lesly Robinson
Felix Sigal
Robert S Kirsner
Mher Vartivarian
Molly Saunders
Jaideep Banerjee
A Multicenter, Randomized, Controlled, Clinical Trial Evaluating a Lyopreserved Amniotic Membrane in the Treatment of Venous Leg Ulcers
Health Science Reports
allografts
amniotic membrane
quality of life
skin substitute
venous ulcers
title A Multicenter, Randomized, Controlled, Clinical Trial Evaluating a Lyopreserved Amniotic Membrane in the Treatment of Venous Leg Ulcers
title_full A Multicenter, Randomized, Controlled, Clinical Trial Evaluating a Lyopreserved Amniotic Membrane in the Treatment of Venous Leg Ulcers
title_fullStr A Multicenter, Randomized, Controlled, Clinical Trial Evaluating a Lyopreserved Amniotic Membrane in the Treatment of Venous Leg Ulcers
title_full_unstemmed A Multicenter, Randomized, Controlled, Clinical Trial Evaluating a Lyopreserved Amniotic Membrane in the Treatment of Venous Leg Ulcers
title_short A Multicenter, Randomized, Controlled, Clinical Trial Evaluating a Lyopreserved Amniotic Membrane in the Treatment of Venous Leg Ulcers
title_sort multicenter randomized controlled clinical trial evaluating a lyopreserved amniotic membrane in the treatment of venous leg ulcers
topic allografts
amniotic membrane
quality of life
skin substitute
venous ulcers
url https://doi.org/10.1002/hsr2.70819
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