A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol

Enrique Gómez-Barrena, Norma G Padilla-Eguiluz, Cristina Avendaño-Solá, Concepción Payares-Herrera, Ana Velasco-Iglesias, Ferran Torres, Philippe Rosset, Florian Gebhard, Nicola Baldini, Juan C Rubio-Suarez, Eduardo García-Rey, José Cordero-Ampuero, Javier Vaquero-Martin, Francisco Chana, Fernando Marco, Javier García-Coiradas, Pedro Caba-Dessoux, Pablo de la Cuadra, Philippe Hernigou, Charles-Henri Flouzat-LachanietteFrançois Gouin, Didier Mainard, Jean Michel Laffosse, Miriam Kalbitz, Ingo Marzi, Norbert Südkamp, Ulrich Stöckle, Gabriela Ciapetti, Davide Maria Donati, Luigi Zagra, Ugo Pazzaglia, Guido Zarattini, Rodolfo Capanna, Fabio Catani

Research output: Contribution to journalArticle

Abstract

ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalStem Cells International
Volume2018
DOIs
Publication statusPublished - Feb 22 2018

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Bone Fractures
Autografts
Biocompatible Materials
Randomized Controlled Trials
Bone and Bones
Arm
Regenerative Medicine
Humerus
Clinical Protocols
Random Allocation
Tibia
Mesenchymal Stromal Cells
Spain
Femur
Italy
France
Germany
Therapeutics
Bone Marrow

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A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol. / Gómez-Barrena, Enrique; Padilla-Eguiluz, Norma G; Avendaño-Solá, Cristina; Payares-Herrera, Concepción; Velasco-Iglesias, Ana; Torres, Ferran; Rosset, Philippe; Gebhard, Florian; Baldini, Nicola; Rubio-Suarez, Juan C; García-Rey, Eduardo; Cordero-Ampuero, José; Vaquero-Martin, Javier; Chana, Francisco; Marco, Fernando; García-Coiradas, Javier; Caba-Dessoux, Pedro; de la Cuadra, Pablo; Hernigou, Philippe; Flouzat-Lachaniette, Charles-Henri; Gouin, François; Mainard, Didier; Laffosse, Jean Michel; Kalbitz, Miriam; Marzi, Ingo; Südkamp, Norbert; Stöckle, Ulrich; Ciapetti, Gabriela; Donati, Davide Maria; Zagra, Luigi; Pazzaglia, Ugo; Zarattini, Guido; Capanna, Rodolfo; Catani, Fabio.

In: Stem Cells International, Vol. 2018, 22.02.2018, p. 1-13.

Research output: Contribution to journalArticle

Gómez-Barrena, E, Padilla-Eguiluz, NG, Avendaño-Solá, C, Payares-Herrera, C, Velasco-Iglesias, A, Torres, F, Rosset, P, Gebhard, F, Baldini, N, Rubio-Suarez, JC, García-Rey, E, Cordero-Ampuero, J, Vaquero-Martin, J, Chana, F, Marco, F, García-Coiradas, J, Caba-Dessoux, P, de la Cuadra, P, Hernigou, P, Flouzat-Lachaniette, C-H, Gouin, F, Mainard, D, Laffosse, JM, Kalbitz, M, Marzi, I, Südkamp, N, Stöckle, U, Ciapetti, G, Donati, DM, Zagra, L, Pazzaglia, U, Zarattini, G, Capanna, R & Catani, F 2018, 'A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol', Stem Cells International, vol. 2018, pp. 1-13. https://doi.org/10.1155/2018/6025918
Gómez-Barrena, Enrique ; Padilla-Eguiluz, Norma G ; Avendaño-Solá, Cristina ; Payares-Herrera, Concepción ; Velasco-Iglesias, Ana ; Torres, Ferran ; Rosset, Philippe ; Gebhard, Florian ; Baldini, Nicola ; Rubio-Suarez, Juan C ; García-Rey, Eduardo ; Cordero-Ampuero, José ; Vaquero-Martin, Javier ; Chana, Francisco ; Marco, Fernando ; García-Coiradas, Javier ; Caba-Dessoux, Pedro ; de la Cuadra, Pablo ; Hernigou, Philippe ; Flouzat-Lachaniette, Charles-Henri ; Gouin, François ; Mainard, Didier ; Laffosse, Jean Michel ; Kalbitz, Miriam ; Marzi, Ingo ; Südkamp, Norbert ; Stöckle, Ulrich ; Ciapetti, Gabriela ; Donati, Davide Maria ; Zagra, Luigi ; Pazzaglia, Ugo ; Zarattini, Guido ; Capanna, Rodolfo ; Catani, Fabio. / A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol. In: Stem Cells International. 2018 ; Vol. 2018. pp. 1-13.
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abstract = "ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.",
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T1 - A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol

AU - Gómez-Barrena, Enrique

AU - Padilla-Eguiluz, Norma G

AU - Avendaño-Solá, Cristina

AU - Payares-Herrera, Concepción

AU - Velasco-Iglesias, Ana

AU - Torres, Ferran

AU - Rosset, Philippe

AU - Gebhard, Florian

AU - Baldini, Nicola

AU - Rubio-Suarez, Juan C

AU - García-Rey, Eduardo

AU - Cordero-Ampuero, José

AU - Vaquero-Martin, Javier

AU - Chana, Francisco

AU - Marco, Fernando

AU - García-Coiradas, Javier

AU - Caba-Dessoux, Pedro

AU - de la Cuadra, Pablo

AU - Hernigou, Philippe

AU - Flouzat-Lachaniette, Charles-Henri

AU - Gouin, François

AU - Mainard, Didier

AU - Laffosse, Jean Michel

AU - Kalbitz, Miriam

AU - Marzi, Ingo

AU - Südkamp, Norbert

AU - Stöckle, Ulrich

AU - Ciapetti, Gabriela

AU - Donati, Davide Maria

AU - Zagra, Luigi

AU - Pazzaglia, Ugo

AU - Zarattini, Guido

AU - Capanna, Rodolfo

AU - Catani, Fabio

PY - 2018/2/22

Y1 - 2018/2/22

N2 - ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

AB - ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

U2 - 10.1155/2018/6025918

DO - 10.1155/2018/6025918

M3 - Article

C2 - 29535772

VL - 2018

SP - 1

EP - 13

JO - Stem Cells International

JF - Stem Cells International

SN - 1687-966X

ER -