WR279,396, a third generation aminoglycoside ointment for the treatment of Leishmania major cutaneous leishmaniasis: a phase 2, randomized, double blind, placebo controlled study
| Autor: | Afif Ben Salah, Nabil Bel Haj Hamida, Koussay Dellagi, Pierre Buffet, Nissaf Ben Alaya, Amor Zâatour, Zaher El Ahmadi, Matthew Downs, Gloria Morizot, Philip L. Smith, Nathalie Ben Massoud, Max Grogl |
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| Přispěvatelé: | Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur [Paris] (IP), Direction Régionale de la Santé de Sidi Bouzid, Direction Régionale de la Santé, Statistics Collaborative, U.S. Army Medical Materiel Development Activity, Fort Detrick, Walter Reed Army Institute of Research, Sponsor: The Office of the Surgeon General (OTSG), Chief, Human Subjects Protection Division, U.S. Army MRMC, Fort Detrick, MD 21702-5012. IND 50,098 HSRRB Protocol #1791. Co-sponsor: Institute Pasteur, Rue du Dr. Roux, Paris, France., Institut Pasteur [Paris] |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Paromomycin
Paromomycin [SDV]Life Sciences [q-bio] Placebo-controlled study Infectious Diseases/Skin Infections law.invention Ointments Placebos 0302 clinical medicine MESH: Leishmania major Randomized controlled trial law MESH: Child MESH: Ointments Leishmania major MESH: Double-Blind Method MESH: Trypanocidal Agents Child MESH: Treatment Outcome MESH: Aged 0303 health sciences MESH: Middle Aged biology lcsh:Public aspects of medicine Aminoglycoside MESH: Aminoglycosides Middle Aged Trypanocidal Agents 3. Good health Infectious Diseases Treatment Outcome MESH: Young Adult Child Preschool Gentamicin France MESH: Tunisia medicine.drug Research Article Infectious Diseases/Tropical and Travel-Associated Diseases Adult medicine.medical_specialty lcsh:Arctic medicine. Tropical medicine Tunisia MESH: Gentamicins Adolescent lcsh:RC955-962 030231 tropical medicine MESH: Placebos Leishmaniasis Cutaneous 03 medical and health sciences Young Adult Cutaneous leishmaniasis Double-Blind Method medicine Humans Aged MESH: Adolescent MESH: Humans 030306 microbiology business.industry MESH: Child Preschool Public Health Environmental and Occupational Health Infectious Diseases/Protozoal Infections Leishmaniasis lcsh:RA1-1270 MESH: Adult biology.organism_classification medicine.disease MESH: Leishmaniasis Cutaneous Dermatology Surgery MESH: France Aminoglycosides Infectious Diseases/Neglected Tropical Diseases Gentamicins business |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, 2009, 3 (5), pp.e432. ⟨10.1371/journal.pntd.0000432⟩ PLoS Neglected Tropical Diseases, Public Library of Science, 2009, 3 (5), pp.e432. ⟨10.1371/journal.pntd.0000432⟩ Scopus-Elsevier PLoS Neglected Tropical Diseases, Vol 3, Iss 5, p e432 (2009) |
| ISSN: | 1935-2727 1935-2735 |
| Popis: | Background Cutaneous leishmaniasis (CL) is a disfiguring disease that confronts clinicians with a quandary: leave patients untreated or engage in a complex or toxic treatment. Topical treatment of CL offers a practical and safe option. Accordingly, the treatment of CL with WR279,396, a formulation of paromomycin and gentamicin in a hydrophilic base, was investigated in a phase 2 clinical study in Tunisia and France. Methods A phase 2, randomized, double blind, vehicle-controlled study was conducted to assess the safety and efficacy of topical WR279,396 when applied twice a day for 20 days as treatment for parasitologically confirmed CL. The study protocol established the primary efficacy end point as complete clinical response (CCR) defined as 50% or greater reduction in the ulceration size of an index lesion by day 50 (D50) followed by complete re-epithelialization by D100, and no relapse through D180. Results Ninety-two subjects were randomized. Leishmania major was identified in 66 of 68 isolates typed (97%). In the intent-to-treat population, 47 of 50 WR279,396 treated participants (94%) met the definition of CCR, compared with 30 of 42 vehicle-placebo participants (71%) [p = 0.0045]. Erythema occurred in 30% and 24% of participants receiving WR279,396 and placebo, respectively [p = 0.64]. There was no clinical or laboratory evidence of systemic toxicity. Conclusion Application of WR279,396 for 20 days was found to be safe and effective in treating L. major CL, and offers great potential as a new, simple, easily applicable, and inexpensive topical therapy for this neglected disease. Trial Registration ClinicalTrials.gov NCT00703924 Author Summary Cutaneous leishmaniasis is due to a small parasite (Leishmania) that creates disfiguring sores, and affects more than one million persons (mainly children) each year. Treating lesions with a cream—instead of with injections as currently done—would greatly improve the well-being of affected patients. No cream formulation that would be efficient and would not create important skin irritation has been identified yet. Here, we tested a new cream formulation (WR279,396) containing paromomycin and gentamicin, two members of a well-known family of antibacterial antibiotics (aminoglycosides). Injectable paromomycin is efficient in other forms of the disease (visceral leishmaniasis). This was a carefully monitored study (phase 2) involving mainly children in Tunisia and France. The cream was applied twice a day for 20 days. The proportion of patients treated with the paromomycin-containing cream (active formulation) that cured (94%) was higher than that observed (71%) in patients treated with a cream that did not contain the active product (placebo formulation). Local irritation affected less than one-third of the patients and was usually mild. This new cream formulation was safe and effective in treating cutaneous leishmaniasis, thereby providing a new, simple, easily applicable, and inexpensive treatment for this neglected disease. |
| Databáze: | OpenAIRE |
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