Hemoporfin Photodynamic Therapy for Port-Wine Stain: A Randomized Controlled Trial

PLoS One. 2016 May 26;11(5):e0156219. doi: 10.1371/journal.pone.0156219. eCollection 2016.

Abstract

Background and objectives: Photodynamic therapy (PDT) has shown potentially beneficial results in treating port-wine stain, but its benefit-risk profile remains undefined. This study aimed to evaluate the efficacy and safety of PDT conducted with hemoporfin and a 532 nm continuous wave laser to treat port-wine stain clinically.

Patients and methods: This randomized clinical trial was conducted in eight hospitals in China. Participants were adolescent and adult patients (age range: 14-65 years old) with port-wine stain. During stage 1 (day 1 to week 8) all patients were randomized at a 3:1 ratio to treatment (532 nm laser irradiation (96-120 J/cm2) with hemoporfin (5mg/kg; PDT-hemoporfin, n = 330)) or placebo groups (irradiation with placebo (PDT-placebo, n = 110)); during stage 2 (week 8 to 16) patients in both groups were offered treatment. Clinician-evaluators, who were blind to the study, classified each case on the following four-level scale according to assessment of before and after standardized pictures of the lesion area: no improvement: <20%; some improvement: 20-59%; great improvement: 60-89%; or nearly completely resolved: ≥90%. The primary efficacy endpoint was proportion of patients achieving at least some improvement at week 8. The secondary efficacy endpoints were proportion of patients achieving nearly completely resolved or at least great improvement at week 8, proportion of patients achieving early completely resolved, at least great improvement, or at least some improvement at week 16, and the corresponding satisfaction of the investigators and the patients (designated as 'excellent', 'good', 'moderate', or 'ineffective') at weeks 8 and 16.

Results: Compared to the PDT-placebo group, the PDT-hemoporfin group showed a significantly higher proportion of patients that achieved at least some improvement (89.7% [n = 295; 95% CI, 85.9%-92.5%] vs. 24.5% [n = 27; 95% CI, 17.4%-33.3%]) at week 8 (P < 0.0001) and higher improvements for all secondary efficacy endpoints. Treatment reactions occurred in 99.5% (n = 731; 95% CI, 98.7%-99.8%) of the PDT-hemoporfin treatments (n = 735). Hyperpigmentation occurred in 22.9 per 100 patient-treatments (n = 168; 95% CI, 20.0-26.0) in the PDT-hemoporfin treated patients.

Conclusions: Hemoporfin-mediated PDT is an effective and safe treatment option for adolescent and adult patients with port-wine stain.

Trial registration: Chinese Clinical Trial Registry ChiCTR-TRC-08000213.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • China
  • Double-Blind Method
  • Female
  • Hematoporphyrins / therapeutic use*
  • Humans
  • Low-Level Light Therapy
  • Male
  • Middle Aged
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use*
  • Port-Wine Stain / drug therapy*
  • Port-Wine Stain / pathology
  • Treatment Outcome
  • Young Adult

Substances

  • Hematoporphyrins
  • Photosensitizing Agents
  • hematoporphyrin monomethyl ether

Grants and funding

This study was co-sponsored by Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. and the Chinese PLA General Hospital, and was funded by the former. The sponsors had no role in the collection, management, or analysis of the data, or interpretation of the data, preparation of the manuscript, or decision to submit the manuscript for publication. In collaboration with the academic coauthors, both cosponsors were involved in the design of the study. The funder was involved in the conduct of the study and reviewed the manuscript prior to submission, and provided support in the form of salaries for authors [JN Tao], but did not have any additional role in the data collection and analysis, decision to publish, or preparation of the manuscript.