González-Andrades, MiguelMata, RosarioGonzález-Gallardo, María del CarmenMedialdea, SantiagoArias-Santiago, SalvadorMartínez-Atienza, JulianaRuiz-García, AntonioPérez-Fajardo, LorenaLizana-Moreno, AntonioGarzón, IngridCampos, AntonioAlaminos, MiguelCarmona, GloriaCuende, Natividad2020-05-152020-05-152017-09-24González-Andrades M, Mata R, González-Gallardo MdC, Medialdea S, Arias-Santiago S, Martínez-Atienza J, et al. A study protocol for a multicentre randomised clinical trial evaluating the safety and feasibility of a bioengineered human allogeneic nanostructured anterior cornea in patients with advanced corneal trophic ulcers refractory to conventional treatment. BMJ Open. 2017; 7:e016487. doi:10.1136/ bmjopen-2017-016487http://hdl.handle.net/10668/3114Introduction There is a need to find alternatives to the use of human donor corneas in transplants because of the limited availability of donor organs, the incidence of graft complications, as well as the inability to successfully perform corneal transplant in patients presenting limbal deficiency, neo-vascularized or thin corneas, etc. We have designed a clinical trial to test a nanostructured fibrin-agarose corneal substitute combining allogeneic cells that mimics the anterior human native cornea in terms of optical, mechanical and biological behaviour. Methods and analysis This is a phase I-II, randomised, controlled, open-label clinical trial, currently ongoing in ten Spanish hospitals, to evaluate the safety and feasibility, as well as clinical efficacy evidence, of this bioengineered human corneal substitute in adults with severe trophic corneal ulcers refractory to conventional treatment, or with sequelae of previous ulcers. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 45 days, receiving the bioengineered corneal graft. In the second phase of the trial (currently ongoing), subjects are block randomised (2:1) to receive either the corneal graft (n=10), or amniotic membrane (n=5), as the control treatment. Adverse events, implant status, infection signs and induced neovascularization are evaluated as determinants of safety and feasibility of the bioengineered graft (main outcomes). Study endpoints are measured along a follow-up period of 24 months, including 27 post-implant assessment visits according to a decreasing frequency. Intention to treat, and per protocol, and safety analysis will be performed. Ethics and dissemination The trial protocol received written approval by the corresponding Ethics Committee and the Spanish Regulatory Authority and is currently recruiting subjects. On completion of the trial, manuscripts with the results of phases I and II of the study will be published in a peer-reviewed journal. Trial registration CT.gov identifier: NCT01765244 (Jan2013). EudraCT number: 2010-024290-40 (Dec2012).enCorneal transplantationCorneal ulcerStromal fibrosisLimbal stem cell deficiencyTissue bioengineeringRandomized controlled trialTransplante de córneaÚlcera de la corneaIngeniería de tejidosEnsayo clínico controlado aleatorioMedical Subject Headings::Persons::Persons::Age Groups::AdultMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control StudiesMedical Subject Headings::Diseases::Eye Diseases::Corneal DiseasesMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Fibroblasts::Corneal KeratocytesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Tissue Transplantation::Corneal TransplantationMedical Subject Headings::Anatomy::Tissues::Epithelium::Epithelium, CornealMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Pilot ProjectsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Culture Techniques::Cell Engineering::Tissue EngineeringMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcomeresearch article28947445open access10.1136/bmjopen-2017-0164872044-6055PMC5623476