District of Columbia
Leishmanias is a disease caused by the bite of sandflies and is found in many parts of the
world including the Europe, Southwest Asia, Africa and the Middle East. This disease is a
threat for military soldiers in areas where this disease is found. Sodium stibogluconate
(SSG) or Pentostam (Glaxo Smith Kline, United Kingdom) is an Investigational New Drug (IND)
product used by the Department of Defense for over 20 years to treat cutaneous, mucosal and
visceral leishmanias. This drug is not licensed for commercial use in the United States
because of very limited need for the product in the U.S.A. The primary objective of this
protocol is to collect safety and efficacy data on the use of Pentostam for treatment of
laboratory-confirmed leishmaniasis with SSG 20mg/kg/d IV for 10 days or 20 days and visceral
and mucocutaneous leishmaniasis with SSG 20mg/kg/d IV for 28 days.
Leishmaniasis is a protozoal disease transmitted by sandflies and is endemic in many parts
of the world including Central and South America, Europe, Southwest Asia, Africa, and the
Middle East. Infected humans may develop cutaneous (Old or New World), mucocutaneous (New
World), or visceral leishmaniasis. The disease is a medical threat for military soldiers
assigned in endemic areas and currently a major cause of morbidity in soldiers deployed to
the Middle East and a complication of military exercises in Panama, Honduras, and South
America. Sodium stibogluconate (SSG) is an Investigational New Drug (IND) product that has
been in use by the Department of Defense (DoD) for over 20 years for the treatment of
cutaneous, mucosal and visceral leishmaniasis. The primary objective of this protocol is to
treat laboratory-confirmed leishmaniasis with SSG 20mg/kg/d intravenously (IV) for 10 days
or 20 days; visceral leishmaniasis will be treated with SSG 20mg/kg/d IV for 28 days as a
second line of therapy for those failing or intolerant of Ambisome; and mucosal
leishmaniasis will be treated with SSG 20mg/kg/d IV for 28 days. Subjects will be monitored
daily and outcome measured at the end of therapy by the degree of healing of cutaneous
lesions or resolution of laboratory abnormalities and symptoms in the case of mucosal and
Pentavalent antimonials (Pentostam, Glaxo Smith Kline, United Kingdom) has been used to
treat leishmaniasis for more than 50 years. This drug has not been licensed for commercial
use in the United States, likely because of limited commercial marketability. Worldwide and
within the DoD, there is a great deal of experience and use of Pentostam for the treatment
of leishmaniasis. SSG is a pentavalent antimony (Sb) complexed to a carbohydrate whose exact
structure and mechanism of action are not known. It is provided as a 100 mg antimony/mL
solution that contains a preservative, m-chlorocresol. The kidneys excrete most of the dose
within 24 hours. In 1984, the World Health Organization recommended the daily dose of
antimony in the treatment of visceral leishmaniasis to be increased to 20 mg/kg/day. A
randomized controlled trial of 40 subjects with American, New World, cutaneous leishmaniasis
(ACL) found 100% cure rates with 20 mg/kg/day Sb for 20 days but only a 76% cure if 10
mg/kg/day for 10 days was used. A comparison of three treatment schedules in 36 subjects
with CL (single rapid infusion, continuous 24 hour infusion, or every eight hour doses)
found no advantage over using once daily dosing. A review of the controlled trials of SSG
concludes that a recommended course of therapy is 20 mg/kg/day with no upper limit to dose
for 20 days for CL and 20 mg/kg/day for 28 days for visceral or mucocutaneous leishmaniasis.
The Pentostam® package insert suggests that 10-20 mg/kg/day with a maximum dose of 850 mg
for a minimum of 20 days be used; however, based on the Centers for Disease Control and
Prevention (CDC) and Walter Reed Army Medical Center (WRAMC) experience and their practice
guidelines, 20 mg/kg/day with no upper limit to dosage is used. In this protocol there will
be no upper limit to the dose. WRAMC recently published their CL treatment experience
primarily in New World leishmaniasis comparing SSG 20 mg/kg for 10 or 20 days and found 100%
of volunteers in the 10-day group were cured. In this study 15% were Leishmania major
infections. Comparable results are expected for Old World leishmaniasis based on clinical
experience and current literature.
Detailed toxicity data for the 20 mg/kg/day dose are provided by several studies.
Percentages from the WRAMC experience are included here. Subjective musculoskeletal
complaints are common (58%), as well as elevated hepatocellular (67%) and pancreatic enzyme
levels (97%) and nonspecific electrocardiogram (EKG) changes (T wave changes). These side
effects are usually reversible, and no deaths have been associated with SSG at WRAMC. Other
SSG toxic effects include headache (22%), rash (9%), thrombocytopenia, depression of various
hematologic cell lines (44%), phlebitis, anaphylaxis, inflammation around lesions, and
transient coughing after infusion. Other associated symptoms include anorexia, malaise,
myalgia, abdominal pain, headache, lethargy, sweating, vertigo, facial flushing, initial
worsening of skin lesions, epistaxis, jaundice and peripheral neuropathy. In our
above-mentioned 10 versus 20 days study, the adverse events (AE) were significantly
decreased in the cohort receiving the 10 days versus 20 with myalgias in 42% (versus 68%),
with less chemical pancreatitis and fewer hematologic parameter disorders. Angioedema during
SSG infusion has recently been described in two subjects at WRAMC. Both subjects responded
quickly to benadryl treatment without complications. Both subjects were subsequently skin
tested with SSG intradermally for hypersensitivity and one reacted.
Alternative heat therapies have been used to successfully treat CL. Laboratory investigation
showed that Leishmania infection is sensitive to heat. Various forms of heat application in
human CL has shown variable efficacy. The TTI Thermomed™ device is currently U.S. Food and
Drug Administration (FDA), section 510-K cleared for use in the treatment of CL. This device
uses localized current field radio frequency. Other therapies that may be effective for
treating CL include topical paromomycin and oral fluconazole.
1. DoD healthcare beneficiary of any age and gender.
2. Clinicoepidemiologic or parasitologic diagnosis (microscopy, PCR or culture) of
3. Able to provide informed consent or assent (children).
4. All participants (both male and female) must agree to take precautions not to become
pregnant or father a child for at least 2 months after receiving SSG.
1. Pregnancy. Females of childbearing potential must have negative urine human chorionic
gonadotropin hormone (HCG) within 96 hours start of infusion period.
2. History of hypersensitivity to pentavalent antimonials.
3. Any of the following on screening examination:
1. QTc interval greater or equal to 0.5 sec
2. Severe cardiac disease (disabling valvular heart disease, myopathy, or
3. History of recurrent pancreatitis
4. Liver failure or active hepatitis with transaminases > 3x upper limit of normal
5. Renal failure or creatinine > 2.5 mg/dL
6. Thrombocytopenia (platelets <100,000/mm^3)
7. White blood cell count < 2000 / mm^3
8. Hematocrit < 30 %