Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies
| Autor: | Jonathan A L Duncan, Gaynor James, Jonquille Chantrey, Sharon O'kane, Anna Ludlow, Tracey Mason, Karen So, Nick Occleston, Hugh G. Laverty, Abdul Sattar, Lisa D. Taylor, Mark W. J. Ferguson, James Bush, Piyush Durani, Jeremy S Bond |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Erythema Adolescent Injections Intradermal Visual analogue scale Biopsy Chemistry Pharmaceutical Premedication Scars Placebo Severity of Illness Index Drug Administration Schedule Statistics Nonparametric law.invention Wound care Cicatrix Young Adult Transforming Growth Factor beta3 Randomized controlled trial Double-Blind Method law medicine Edema Humans Adverse effect Aged Aged 80 and over Analysis of Variance Wound Healing Intention-to-treat analysis business.industry General Medicine Middle Aged Surgery Treatment Outcome Female medicine.symptom business |
| Zdroj: | Lancet (London, England). 373(9671) |
| ISSN: | 1474-547X 0084-7925 |
| Popis: | Summary Background Research into mechanisms of skin scarring identified transforming growth factor β3 (TGFβ3) as a potential antiscarring therapy. We assessed scar improvement with avotermin (recombinant, active, human TGFβ3). Methods In three double-blind, placebo-controlled studies, intradermal avotermin (concentrations ranging from 0·25 to 500 ng/100 μL per linear cm wound margin) was administered to both margins of 1 cm, full-thickness skin incisions, before wounding and 24 h later, in healthy men and women. Treatments (avotermin and placebo or standard wound care) were randomly allocated to wound sites by a computer generated randomisation scheme, and within-participant controls compared avotermin versus placebo or standard wound care alone. Primary endpoints were visual assessment of scar formation at 6 months and 12 months after wounding in two studies, and from week 6 to month 7 after wounding in the third. Investigators, participants, and scar assessors were blinded to treatment. Efficacy analyses were intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00847925, NCT00847795, and NCT00629811. Results In two studies, avotermin 50 ng/100 μL per linear cm significantly improved median score on a 100 mm visual analogue scale (VAS) by 5 mm (range −2 to 14; p=0·001) at month 6 and 8 mm (−29 to 18; p=0·0230) at month 12. In the third, avotermin significantly improved total scar scores at all concentrations versus placebo (mean improvement: from 14·84 mm [95 % CI 5·5–24·2] at 5 ng/100 μL per linear cm to 64·25 mm [49·4–79·1] at 500 ng/100 μL per linear cm). Nine [60%] scars treated with avotermin 50 ng/100 μL per linear cm showed 25% or less abnormal orientation of collagen fibres in the reticular dermis versus five [33%] placebo scars. After only 6 weeks from wounding, avotermin 500 ng/100 μL per linear cm improved VAS score by 16·12 mm (95% CI 10·61–21·63). Adverse events at wound sites were similar for avotermin and controls. Erythema and oedema were more frequent with avotermin than with placebo, but were transient and deemed to be consistent with normal wound healing. Interpretation Avotermin has potential to provide an accelerated and permanent improvement in scarring. Funding Renovo (UK). |
| Databáze: | OpenAIRE |
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