Abstract

Background The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. Objectives To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 21 July 2014; date of the last search of the Cochrane Wounds Group Trials Register: 18 September 2014. Selection criteria Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. Data collection and analysis Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. Main results Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl (R) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69; very low quality of evidence). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix; ranging between low and very low quality of evidence). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. Authors' conclusions There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports. We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses. This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.