Kaoru Omae1, Shin-Ichi Kanemaru2, Eiji Nakatani3, Hideaki Kaneda4, Tsutomu Nishimura5, Risa Tona6, Yasushi Naito7, Atsuhiko Kawamoto8, Masanori Fukushima9. 1. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: k-omae@tri-kobe.org. 2. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Otolaryngology, Head and Neck Surgery, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Otolaryngology, Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan. Electronic address: kanemaru@ent.kuhp.kyoto-u.ac.jp. 3. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: e-nakatani@tri-kobe.org. 4. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: hkaneda@tri-kobe.org. 5. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: t-nishimura@tri-kobe.org. 6. Department of Otolaryngology, Head and Neck Surgery, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Otolaryngology, Head and Neck Surgery, Kobe City Medical Center General Hospital, 2-2-1 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: tona_risa@ent.kuhp.kyoto-u.ac.jp. 7. Department of Otolaryngology, Head and Neck Surgery, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Otolaryngology, Head and Neck Surgery, Kobe City Medical Center General Hospital, 2-2-1 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: naito@kcho.jp. 8. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Unit of Regenerative Medicine, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: kawamoto@fbri.org. 9. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: mfukushi@tri-kobe.org.
Abstract
OBJECTIVE: The objective of this study was to evaluate safety and efficacy of regenerative treatment using gelatin sponge with basic fibroblast growth factor (bFGF) in patients with tympanic membrane perforation (TMP). METHODS: The current study was a prospective, multicenter, open-label, single-arm, and exploratory clinical trial to evaluate the safety and efficacy of the TM regeneration procedure (TMRP). Myringotomy was used to mechanically disrupt the edge of the TMP, and a gelatin sponge immersed in bFGF was then placed over the perforation. Fibrin glue was dripped over the sponge as a sealant. TMP closure was examined 4 weeks later and, if insufficient, TMRP was repeated a maximum of three more times. TMP closure and hearing improvement 12 weeks after the final TMRP as well as safety were evaluated. RESULTS: Of the 11 patients with TMP who participated in this study, one who fulfilled the exclusion criteria and did not undergo TMRP and one with cholesteatoma were excluded from the efficacy analysis. TMP closure and hearing improvement 12 weeks after the final TMRP were achieved in eight out of nine patients (88.9%). Mean bone conduction threshold significantly improved 12 weeks after the TMRP compared with baseline (35.7±20.3 vs 29.4±21.0dB, P=0.015). Six out of ten patients receiving TMRP experienced temporary adverse events: appendicitis (serious, severe), otorrhea (mild), otitis media (mild), and sudden hearing loss (mild). However, none were related to the protocol treatment. CONCLUSION:TMP closure and hearing improvement were frequently confirmed following the TMRPs which were safely performed. These favorable outcomes were accompanied with significant improvement of the bone conduction threshold. These promising outcomes would encourage a large-scaled, randomized and pivotal clinical trial in the future. This trial is registered at http://www.umin.ac.jp/ctr/index.htm (identifier: UMIN000006585).
RCT Entities:
OBJECTIVE: The objective of this study was to evaluate safety and efficacy of regenerative treatment using gelatin sponge with basic fibroblast growth factor (bFGF) in patients with tympanic membrane perforation (TMP). METHODS: The current study was a prospective, multicenter, open-label, single-arm, and exploratory clinical trial to evaluate the safety and efficacy of the TM regeneration procedure (TMRP). Myringotomy was used to mechanically disrupt the edge of the TMP, and a gelatin sponge immersed in bFGF was then placed over the perforation. Fibrin glue was dripped over the sponge as a sealant. TMP closure was examined 4 weeks later and, if insufficient, TMRP was repeated a maximum of three more times. TMP closure and hearing improvement 12 weeks after the final TMRP as well as safety were evaluated. RESULTS: Of the 11 patients with TMP who participated in this study, one who fulfilled the exclusion criteria and did not undergo TMRP and one with cholesteatoma were excluded from the efficacy analysis. TMP closure and hearing improvement 12 weeks after the final TMRP were achieved in eight out of nine patients (88.9%). Mean bone conduction threshold significantly improved 12 weeks after the TMRP compared with baseline (35.7±20.3 vs 29.4±21.0dB, P=0.015). Six out of ten patients receiving TMRP experienced temporary adverse events: appendicitis (serious, severe), otorrhea (mild), otitis media (mild), and sudden hearing loss (mild). However, none were related to the protocol treatment. CONCLUSION: TMP closure and hearing improvement were frequently confirmed following the TMRPs which were safely performed. These favorable outcomes were accompanied with significant improvement of the bone conduction threshold. These promising outcomes would encourage a large-scaled, randomized and pivotal clinical trial in the future. This trial is registered at http://www.umin.ac.jp/ctr/index.htm (identifier: UMIN000006585).