Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial.
BACKGROUND
Alternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India.


METHODS
A multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa. Patients aged 4-60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE) data.


RESULTS
The PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002). The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: -1.3 to 6.3%, p = 0.198). End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens.


CONCLUSIONS
The 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa.


BACKGROUND
www.clinicaltrials.govNCT00255567.
Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Ahmed
A
Musa
Eltahir
E
Khalil
Asrat
A
Hailu
Joseph
J
Olobo
Manica
M
Balasegaram
Raymond
R
Omollo
Tansy
T
Edwards
Juma
J
Rashid
Jane
J
Mbui
Brima
B
Musa
Abuzaid Abdalla
AA
Abuzaid
Osama
O
Ahmed
Ahmed
A
Fadlalla
Ahmed
A
El-Hassan
Marius
M
Mueller
Geoffrey
G
Mucee
Simon
S
Njoroge
Veronica
V
Manduku
Geoffrey
G
Mutuma
Lilian
L
Apadet
Hudson
H
Lodenyo
Dedan
D
Mutea
George
G
Kirigi
Sisay
S
Yifru
Getahun
G
Mengistu
Zewdu
Z
Hurissa
Workagegnehu
W
Hailu
Teklu
T
Weldegebreal
Hailemariam
H
Tafes
Yalemtsehay
Y
Mekonnen
Eyasu
E
Makonnen
Serah
S
Ndegwa
Patrick
P
Sagaki
Robert
R
Kimutai
Josephine
J
Kesusu
Rhoda
R
Owiti
Sally
S
Ellis
Monique
M
Wasunna
D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage* / Q000009:adverse effects; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010303:Paromomycin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
D000981:Antiprotozoal Agents; D010303:Paromomycin; D000967:Antimony Sodium Gluconate