The exact incidence of LC is not known. For nearly 80 years, pentavalent antimony compounds: sodium stibogluconate (Pentostan®, produced by Glaxo-Wellcome) and meglumine antimoniate (Glucantime®, produced by Sanofi-Aventis) have been considered the first choice treatments for this disease despite their toxicity, difficult administration and high cost. A dose of 20 mg Sb5/kg/day for 20 days administered intramuscularly or parenterally is recommended in adult patients diagnosed with LC caused by L. braziliensis, L. panamensis, L. amazonensis, L. peruviana or L. mexicana. Pentavalent antimonials have many disadvantages such as parenteral administration and reversible side effects such as nausea, vomiting, muscle and abdominal pain, cardiac problems, increased hepatic aminotransferase concentration and chemical pancreatitis. In addition, adherence to treatment is affected by its duration (several weeks) and its availability due to restrictions on its distribution.
Since 2005, Miltefosine (hexadecylphosphocholine), an oral drug, has been proposed as the drug of first choice, especially in children diagnosed with LC caused by L. panamensis, L. mexicana, L. guyanensis or L. braziliensis; however, because it is potentially teratogenic, it is contraindicated during pregnancy and requires appropriate counseling of female patients of childbearing age and their partners in order to avoid pregnancies up to two months after the end of treatment. A dose of 50 mg for 28 days is recommended.
It is currently recommended to apply local treatments for patients with localized LC, either with pentavalent antimonials administered intralesionally or with thermotherapy. It is important to note that it is not mandatory to identify the Leishmania species to initiate treatment; however, if the most prevalent species in the region is known, treatment should be initiated according to the clinical condition of the patient, the availability of the drug and the risk-benefit balance.
PAHO recommends the use of local treatments for LC in situations in which the patient presents between 1 to 3 lesions, located in any area (except the head and periarticular areas), each lesion with an area of up to 900 mm2, with the absence of immunosuppression and the possibility of follow-up.
Arnica montana L. is a plant belonging to the Asteraceae family, which is composed of 28 to 32 species. This plant is endemic to central and southern Europe (Pyrenees and Alps), southern Scandinavia and northern Spain. It is a medicinal plant of ancestral use, recognized by several countries to alleviate various ailments. Its variety of indications can be explained by the production of a large amount of secondary metabolites such as sesquiterpene lactones (LST), flavonoids or phenolic acids. It has been demonstrated that arnica LSTs permeate through porcine skin and human skin, most of them (97%) are absorbed after 48 h and are retained in the skin, binding irreversibly to skin proteins, accumulating in the epidermis; suggesting that they do not reach systemic circulation being a safer and more beneficial treatment at local level.
The main indication corresponds to its anti-inflammatory activity. Helenalin-like LST (HL) and 11-α-13 dihydrohelenalin (DHL) are the constituents responsible for this effect, since these molecules decrease inflammation mediated by the transcription factor NF-kB. Additionally, there are other properties demonstrated in the literature such as antioxidant, antimicrobial or insecticidal activities.
Arnica tincture is a topical preparation based on the plant legally authorized in the countries of the European community and is included in the vademecun of medicinal plants in Colombia. The product under investigation is the commercial phytotherapeutic product Arnica Tintura Gehrlicher 100 mL manufactured by Gehrlicher Pharmazeutische Extrakte GmbH. According to the European Pharmacopoeia, the solution is a 70% hydroethanolic tincture prepared from the flowers of Arnica montana L., and compounded with at least 0.04% sesquiterpene lactones.
A randomized phase Ib/II clinical trial conducted in patients with localized LC in Colombia showed an efficacy of 100% (per protocol analysis) and 92% (intention-to-treat analysis), with no adverse effects other than those expected such as erythema, burning, pain or pruritus.
1. Main objectives
* To evaluate the safety of arnica tincture in individuals with localized LC, by measuring occurrence and severity analysis of Adverse Effects (AEs), compared to treatment with pentavalent antimonials administered intralesionally.
* To evaluate the efficacy of arnica tincture in individuals with localized LC, according to the percentage of individuals and number of lesions with clinical healing corresponding to day 90 post-treatment, compared to treatment with pentavalent antimonials administered intralesionally.
2. Secondary objectives.
* To evaluate the frequency and severity of AEs associated with the use of arnica tincture compared to treatment with intralesionally administered pentavalent antimonials.
* To evaluate the status of lesions over time to evidence of complete epithelialization/flattening of lesions, proportion of individuals with 100% epithelialization/flattening of lesions, and the number of epithelialized/non-indurated lesions in patients treated with tincture of arnica compared to treatment with intralesionally administered pentavalent antimonials.
* To compare the safety and efficacy of arnica tincture with treatment with intralesionally administered pentavalent antimonials.
To evaluate the overall risks and benefits of treatment with arnica tincture compared to treatment with intralesionally administered pentavalent antimonials.
