Table 4.
Summary of studies and clinical trials on LAMB use for VL.
| Country/Author/Ref. | Study design | Regimen used | Indication | Sample size | Efficacy/effectiveness | Comments |
|---|---|---|---|---|---|---|
| Ethiopia/Ritmeijer et al.; 2011 [24] | Retrospective cohort analysis | LAMB 30 mg/kg split over 6 doses* | A: Severely ill B: HIV/VL +/- relapse |
A: N = 94 B: N = 195 (79 relapses) |
A: IC = 93% B: IC = 60% |
IC among HIV+ relapse patients = 38% |
| India/Sinha et al.; 2011 [28] | Retrospective cohort analysis | LAMB 20 – 25 mg/kg split over 4 – 15 days* | HIV/VL +/- relapse | N = 55 (27 relapses) | Survival at 2 years = 85.5% | Relapse at 1 and 2 years = 8% and 26.5% |
| India/Sundar et al.; 2011 [5] | Phase III non-inferiority RCT | A: ampho B B: LAMB and MF* C: LAMB and PM* D: MF and PM |
Primary uncomplicated VL (e.g., no HIV or severely ill) | A: N = 157 B: N = 160 C: N = 158 D: N = 159 |
A: ITT DC = 93% B: ITT DC = 97.5% C: ITT DC = 97.5% D: ITT DC = 98.7% |
LAMB regimens were single LAMB doses + MF/PM (7 – 10 days) |
| India/Sundar et al.; 2011 [34] | Non-comparative clinical trial | LAMB and MF*
(single dose + 14-day MF) |
Primary uncomplicated VL | N = 135 | ITT DC = 91.9% | Some GI side effects noted with MF use |
| India/Sinha et al.; 2010 [27] | Prospective cohort study | LAMB 20 mg/kg split over 4 doses* | Primary and relapse cases in routine care | N = 251 | DC = 98.8% (lost to follow-up = 17.5%) |
1% of cases experienced lip swelling |
| India/Mondal et al.; 2010 [20] | Open-label dose finding (Phase II) clinical trial | A: LAMB 5 mg/kg B: LAMB 7.5 mg/kg C: LAMB 10 mg/kg (total doses) |
Uncomplicated VL | A: N = 10 B: N = 10 C: N = 10 |
A: ITT DC = 60% (5 people excluded) B: ITT DC = 50% C: ITT DC = 90% |
Fungisome™ (Lifecare) formulation used |
| India/Sundar et al.; 2010 [6] | Phase III non-inferiority RCT | A: ampho B B: LAMB 10 mg/kg single dose* |
Uncomplicated VL | A: N = 108 B: N = 306 |
A: ITT DC = 96.3% B: ITT DC = 95.7% |
Only 1% SAEs (nephro/hepatotoxicity) per group |
| India/Sundar et al.; 2008 [33] | Phase II RCT | A: LAMB 5 mg/kg* B: LAMB 5 mg/kg and MF 10 days* C: LAMB 5 mg/kg and MF 14 days* D: LAMB 3.75 mg/kg and MF 14 days* E: LAMB 5 mg/kg and MF 7 days* |
Uncomplicated VL | A: N = 45 B: N = 46 C: N = 45 D: N = 45 E: N = 45 |
A: ITT = 91% B: ITT = 98% C: ITT = 96% D: ITT = 96% E: ITT = 98% cure rates are at 9 months follow-up for all groups |
All treatments were tolerated to completion, but hepatotoxicity noted especially in group C |
| Spain/Molina et al.; 2007 [19] | Retrospective cohort analysis | LAMB 40 mg/kg total initial Rx + 5 mg/kg secondary prophylaxis* | HIV co-infected relapses cases | N = 17 | Free of relapse: 6 months = 89.7% 12 months = 79.1% 36 months = 55.9% |
Significant increase seen in CD4 count in the non-relapses |
| Sudan/Mueller et al.; 2007 [22] | Retrospective cohort analysis | LAMB 15 – 49 mg/kg given over 6 doses* | 52 relapses and 12 complicated cases | N = 64 | IC = 55% only | TB, HIV, initial parasite density linked with failure |
| Sudan/Mueller et al.; 2006 [21] | Retrospective cohort analysis | A: SSG alone B: SSG and LAMB* C: LAMB alone* |
VL in pregnant women | A: N = 23 B: N = 4 C: N = 12 |
IC = 100% all groups; 13 abortions noted in group A, none in B and C |
LAMB appears safer than SSG in pregnant women with VL |
| India/Sanath et al.; 2005 [25] | Post-marketing cohort study | LAMB 1 – 3 mg/kg/day for 7 – 76 days | Mixed population in routine care | 91 out of 144 assessed for cure | IC = 73.6%, 8.7% had no response |
Fungisome™ (Lifecare) used, no drug-related SAEs noted |
| Greece/Kafetzis et al.; 2005 [18] | Retrospective cohort analysis | A: MA (20 mg/kg for 21 days) B: LAMB varying doses* |
Children under the age of 15 | A: N = 10 B: N = 19 |
All patients initially cured, no relapses noted after | Shorter median hospitalization with LAMB (19 vs 7 days) |
| Italy/Cascio et al.; 2004 [14] | Retrospective cohort analysis | LAMB 3 mg/kg in 6 doses over 10 days* | HIV negative children under the age of 15 | N = 164 | IC = 100% 4.3% relapsed 3 – 15 months after |
All relapses cured with LAMB (total dose 30 mg/kg) |
| India/Sundar et al.; 2004 [32] | Open-label RCT | A: ampho B B: LAMB 2 mg/kg/5 days* |
Uncomplicated VL | A: N = 51 B: N = 51 |
A: ITT DC = 96% B: ITT DC = 96% |
2 patients in group A died, 2 failures in group B |
| India/Sundar et al.; 2003 [30] | Non-comparative clinical trial | LAMB 7.5 mg/kg single dose* | Uncomplicated VL | N = 203 | ITT IC = 96% ITT DC = 90% |
Few AEs noted, mainly infusion reactions |
| Italy/Pagliano et al.; 2003 [23] | Retrospective cohort analysis | A: MA (20 mg/kg for 21 days) B: LAMB 3 mg/kg in 6 doses over 10 days* |
HIV negative adults | A: N = 24 B: N = 40 |
After 2 years post-treatment: A: 12% failures B: 5% failures |
Faster recovery time noted with LAMB |
| Greece/Syriopoulou et al.; 2003 [35] | Prospective study | LAMB 10 mg/kg over 2 days* | HIV negative children | N = 41 | DC = 98% | Fast recovery time, mild infusion related reactions in < 10% of patients |
| India/Sundar et al.; 2002 [31] | Double-blind Phase II RCT | A: LAMB 3.75 mg/kg over 5 days* B: LAMB 7.5 mg/kg over 5 days* A: LAMB 15 mg/kg over 5 days* |
Refractory cases to antimonials | A: N = 28 B: N = 28 C: N = 28 |
A: ITT DC = 89% B: ITT DC = 93% C: ITT DC = 97% |
Mild/moderate infusion-related reactions were common |
| India/Sundar et al.; 2001 [29] | Open-label Phase II RCT | A: LAMB 5 mg/kg single dose* B: LAMB 5 mg/kg over 5 days* |
Uncomplicated VL | A: N = 46 B: N = 45 |
A: ITT DC = 91% B: ITT DC = 93% |
Mild infusion-related reactions were common |
| India/Thakur; 2001 [36] | Open-label RCT | A: LAMB 15 mg/kg single dose* B: ampho B (1 mg/kg × 20 days) |
Uncomplicated VL | A: N = 17 B: N = 17 |
A: ITT DC = 100% B: ITT DC = 100% |
Fewer adverse events noted in the LAMB group |
| India/Bodhe et al.; 1999 [13] | Dosing study (Phase II) clinical trial |
Various doses of LAMB ranging from 1 mg/kg for 21 days to 3 mg/kg for 7 days | Primary and relapse cases | N = 63 | Cure rates varied from 90 to 100% depending on dose | Used L-AMP-LRC 1 (liposome pharmacology center) |
| India, Kenya, Brazil/ Berman et al.; 1998 [12] |
Phase II dose ranging clinical trial | A: LAMB 14 mg/kg total dose* B: LAMB 10 mg/kg total dose* C: LAMB 6 mg/kg total dose* D: LAMB 20 mg/kg total dose (Brazil only)* |
Groups were done sequentially in descending doses; parallel studies done in India, Kenya and Brazil |
A: N = 10 (India, Kenya) N = 13 (Brazil) B: N = 10 (India, Kenya) C: N = 10 (India, Kenya) D: N = 15 (Brazil only) |
India: 100% DC rates in A, B, C Kenya: 100%, 80% and 20% DC in A, B, C Brazil: 62% and 83% DC in groups A and D, respectively |
Differential efficacy seen across 3 continents with India > Kenya ≥ Brazil |
| Italy/di Martino et al.; 1997 [17] | Prospective study | LAMB various doses* | Pediatric population | N = 106 | Up to 100% | 18 mg/kg total identified as the optimum dose |
| Italy, Brazil, UK/ Davidson et al.; 1996 [15] |
Dose decreasing (Phase II) clinical trial | A: LAMB 24 mg/kg total dose* B: LAMB 18 mg/kg total dose* C: LAMB 15 mg/kg total dose* D: LAMB 12 mg/kg total dose* (split into 6 doses) |
Adult and pediatric population Uncomplicated VL |
A: N = 13 B: N = 42 C: N = 32 D: N = 1 |
Cure at 1 year = A: 10/13 (3 LTFU were IC) B: 41/42 (1 relapse) C: 29/32 (1 failure, 2 relapse) D: 1/1 |
Treatment well tolerated with no cessation of treatment; and well tolerated in children |
| Sudan/Seaman et al.; 1995 [26] | Open label, dosing (Phase II) clinical trial | A: LAMB 3 – 5 mg/kg × 3 doses* B: LAMB 3 – 5 mg/kg × 6 doses* C: LAMB 4 – 5 mg/kg × 4 doses* |
Relapse and complicated (severely ill) cases included | A: N = 16 B: N = 16 |
A: 50% cured B: 88% cured C: 64% cured |
Long-term follow-up not done |
| Europe/Davidson et al.; 1994 [16] | Open label, dosing (Phase II) clinical trial | A: LAMB 1 – 1.38 mg/kg × 21 doses* B: LAMB 3 mg/kg × 10 doses* C: LAMB 1.38 – 1.85 mg/kg × 21 doses* |
Gp A and B were immune-competent Gp C was immune-compromised |
A: N = 10 B: N = 10 C: N = 11 |
Cure rates at over 12 months: A: 100% B: 100% C: 27% (100% were IC) |
Groups A and B were largely made up of children; Group C included adults only |
Country denotes where patients were recruited.
*Denotes when AmBisome™ (currently Gilead, previously Vestar) was used.
AE: Adverse event; ampho B: Conventional amphotericin B 15 mg/kg total dose; DC: Definitive cure at 6 months; indication is for type of VL (primary, relapse, HIV co-infected); IC: Initial cure; ITT: Intention to treat; LAMB: Liposomal amphotericin B; MA: Meglumine antimoniate; MF: Miltefosine; PM: Paromomycin; RCT: Randomised controlled trial; SAE: Serious adverse event; VL: Visceral leishmaniasis.