Effectiveness and safety of a mixture of diosmin, coumarin and arbutin (Linfadren®) in addition to conventional treatment, in the management of patients with persistent hand edema following trauma or surgery of distal forearm or hand. A randomized controlled trial.

Once eligible for the trial, participants will be recruited and randomised into one of the following 6-week interventions: 1) conventional rehabilitation treatment (control group) 2) conventional rehabilitation treatment plus Linfadren® (study group) a) conventional rehabilitation treatment consisting of elevation, cryotherapy, low-compression garments, retrograde massage, and gentle hand movement. These treatments were performed once a day for five days a week for six weeks, Patients will receive sessions with retrograde massage and gentle hand movement on a one-to-one basis with an experienced physiotherapist who also monitored the patients' adherence to the other treatments b) Linfadren® is a marketed supplement formulation which contains 200 mg of diosmin, 30.6 mg of coumarin, and 3.7 mg of arbutin. Coumarin (alpha-benzopyrones), stimulating macrophage activation and proteolysis, favors the reduction of excess stagnant proteins from tissues, with a decrease of edema and chronic inflammation. Diosmin (gamma-benzopyrones) is mainly a vascular-protecting agent, improving venous tone, protecting capillary bed microcirculation, reducing capillary permeability, but being potent inhibitors of inflammatory mediators as prostaglandin E2 (PGE2) and thromboxane A2 (TxA2), also exhibits anti-inflammatory properties. Arbutin is a natural product found in different plants including bearberry (Arctostaphylos uva-ursi) and has diuretic properties that help to reduce water tissue retention. Patients were instructed to consume Linfadren® on an empty stomach twice a day (6-hourly: 11a.m. and 5 p.m.) for two weeks, and once a day for four weeks. To improve adherence as far as medication assumption we asked patients to self-compile a daily diary.