Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3 Multicenter, Randomized, Controlled, Clinical Trial to Assess the Safety and Efficacy of Injectable Paromomycin in Patients With Visceral Leishmaniasis
Brief Summary: Symptomatic Visceral Leishmaniasis(VL)is fatal; Due to the increasing resistance to standard therapy with antimonials, there is a need for new safe, efficacious, low-cost therapies for the treatment of VL. Paromomycin is an off-patent aminoglycoside antibiotic with anti-leishmaniasis activity. This study will test the safety and efficacy of paromomycin in the treatment of patients with VL in India.


Options:
A: Inclusion Criteria:

* Age 5-75 years
* Lesions must measure at least 1 cm and be primarily ulcerative
* Have cutaneous leishmaniasis proven parasitologically in the lesion selected for study
* Must have given written informed consent to participate in the study

Exclusion Criteria:

* Known drug intolerance to aminoglycosides in the patient or immediate family
* Previous use of antileishmanial drugs (within 3 months) or present use of routinely nephrotoxic or ototoxic drugs
* Patients with tuberculosis under treatment
* Potential for follow-up: have less than 7 months time remaining in present address and/or plan to leave the area for more than 30 days
* Extent of disease: more than 5 lesions or lesion equal to or greater than 5 cm or a lesion less than 5 cm from the eye, or a lesion in the face that, in the opinion of the attending dermatologist could potentially cause significant disfigurement
* Location of disease: mucosal involvement
* Disseminated disease: clinically significant lymphadenitis with nodules that are painful and greater than 1 cm in size in the lymphatic drainage of the ulcer
* Concomitant medical problems: significant medical problems of the kidney or liver as determined by history and by the following laboratory studies:
* Hearing abnormality
* Ongoing pregnancy or have plans to become pregnant
* Females of child bearing age (Tunisia Only)
* Signs or symptoms of peripheral neuropathy

Kidney: clinically significant abnormalities of urine analysis, serum levels of creatinine, BUN, total proteins greater than the upper limit of normal for the laboratory.

Liver: AST or ALT greater than the upper limit of normal for the laboratory General: glucose, Na+, or K+ greater than the upper limit of normal for the laboratory
B: Inclusion Criteria:

* The subject was age 5 years or older, but less than 65 years.
* The subject was able to understand the information provided to him/her and give written informed consent. Consent was obtained from the parent/guardian of subjects who were \< 18 years old. Children 12 to \< 18 years old were asked to sign the written assent form. Witnessed verbal assent was obtained from subjects 5 to 11 years old.
* The subject was a male or female who was generally healthy.
* The subject had cutaneous lesions diagnosed as leishmaniasis in the index lesion by: (1) the identification of promastigotes in a culture of an aspirated lesion, or (2) the microscopic identification of Leishmania amastigotes on a DifQuik or Giemsa stained smear obtained from a lesion scraping.
* The subject had five or fewer cutaneous lesions.
* The subject had one lesion, which would be designated as the index lesion, that was ≥ 1 and \< 5 cm in its greatest diameter and primarily ulcerative, ie, not purely verrucous or nodular.
* The subject was willing to forego other forms of treatment for CL, including other investigational treatment during the study.
* In the opinion of the principal investigator, the subject or subject's parent/guardian was capable of understanding and complying with the protocol

Exclusion Criteria

* The subject received previous treatment for leishmaniasis (including WR 279,396) within the last 6-months, with the exception of mercurochrome.
* The subject had difficulty complying with instructions on maintaining the dressing, eg, due to life style activities or age.
* The subject had only a single lesion whose characteristics included any of the following: verrucous or nodular lesion, ≥ 5 cm in its greatest diameter, \< 1 cm or located on the ear, or other location that in the opinion of the principal investigator would be difficult to maintain application of study drug topically.
* The subject had a lesion due to Leishmania that involved the mucosa.
* The subject had signs or symptoms of disseminated disease, ie, clinically significant lymphadenitis with nodules that were painful and \> 1 cm in the lymphatic drainage of the ulcer.
* The subject was a female with a positive urine pregnancy test, or who was breast feeding or lactating.
* The subject had an active malignancy or had a history of a solid, metastatic or hematologic malignancy, with the exception of a basal or squamous cell carcinoma of the skin that had been removed.
* The subject had a significant organ abnormality or chronic disease that, in the opinion of the investigator, would warrant exclusion of the subject from the study or would prevent the subject from completing the study.
* The subject was receiving any of the following medications: any medication containing pentavalent antimony, including stibogluconate sodium (Pentostam®) and meglumine antimoniate (Glucantime®); amphotericin B, including liposomal amphotericin B and amphotericin B deoxycholate; other medications containing paromomycin (administered IV or topically); methylbenzethonium chloride, fluconazole, ketoconazole, itraconazole; pentamidine; or allopurinol.
* The subject or the subject's parent/guardian was unable to understand verbal and/or written Arabic, English, or French (languages in which certified translations of the informed consent were available).
* The subject presented with an immuno-compromising condition, including recidivant leishmaniasis (during the past 2 years), or diabetes.
* The subject had a history of known or suspected idiosyncratic reactions or hypersensitivity to aminoglycosides.
C: Inclusion Criteria:

* Age between 5-55 years (inclusive) of either gender.
* Newly diagnosed VL or VL treatment failure confirmed by spleen or bone marrow aspirate.
* Clinical signs and symptoms compatible with VL: fever of over two weeks duration and splenomegaly.
* Biochemical and haematological test values as follows:

  * Haemoglobin \> 5.0g/100mL
  * White blood cell count \> 1 x109/L
  * Platelet count \> 50 x 109/L
  * AST, ALT and alkaline phosphatase \< 3 times upper normal limit
  * Prothrombin time \< 5 seconds above control
  * Serum creatinine levels within normal limits
  * Serum potassium levels within normal limits
* HIV negative

Exclusion Criteria:

* A history of intercurrent or concurrent diseases (e.g. chronic alcohol consumption or drug addiction; renal, hepatic, cardiovascular or central nervous system disease; diabetes; tuberculosis or other infectious or major psychiatric diseases) that may introduce variables affecting the outcome of the study.
* Any condition which the investigator thinks may prevent the patient from completing the study therapy and subsequent follow-up.
* An abnormal baseline audiogram (presentation with 75 dB or higher at 8KHz or below) and/or a history of significant vestibular or auditory dysfunction.
* Proteinuria (\> 2+).
* A history of allergy or hypersensitivity to aminoglycosides.
* A history of major surgery within the last two weeks.
* Pregnancy or lactation. \[Note: women of childbearing age must use an adequate form of contraception (documented) or agree to a period of sexual abstinence during the treatment phase of the study.\]
* Previous treatment for VL within two weeks of enrolment into the study.
* Prior treatment failures with paromomycin or amphotericin B.
D: Inclusion Criteria:

* Department of Defense (DOD) Healthcare beneficiary
* Parasitologic diagnosis of cutaneous Leishmania infection

(Inclusion criteria for randomization includes that must be Leishmania major species)

* Willing to locate to WRAMC area during treatment and perform subsequent follow-up visits if needed

(If not active duty on orders, then the participant will bear the cost of food and lodging during the initial 10-day outpatient treatment period at Walter Reed Army Medical Center)

* Able to provide informed consent
* 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 sodium stibogluconate

Exclusion Criteria:

* Unable to provide informed consent
* Pregnancy (females of child bearing potential must have negative urine human chorionic gonadotropic hormone \[HCG\] within 48 hours of the start of infusion period)
* History of hypersensitivity to pentavalent antimonials
* Serious medical illness:

  1. QTc interval \>/= 0.5 sec
  2. severe cardiac disease
  3. history of current pancreatitis
  4. liver failure or active hepatitis with transaminases \>3X normal
  5. renal failure or creatinine \>2.5
  6. thrombocytopenia (platelets \<75,000)
  7. white blood cell count \<2000
  8. hematocrit \<25
  9. absence of palpable extremity pulses in the limb requiring treatment
* History of serious allergic reaction to local anesthetics
* Location of lesion not amenable to local therapy (such as close to eye, mucous membranes, face, cartilage)
* Presence of pacemaker and/or other implanted metallic devices
* Breast feeding
* Men unwilling to avoid fathering a child during and/or in the two months following receiving the treatment
* Women unwilling to avoid pregnancy for at least two months after receiving the treatment
* More than 20 lesions, or multiple lesions which in the opinion of the investigator would not be well treated with heat therapy

Answer: C