Single-dose liposomal amphotericin B treatment for cryptococcal meningitis

Single-dose liposomal amphotericin B treatment for cryptococcal meningitis. Jarvis, J. N, Lawrence, D. S, Meya, D. B, Kagimu, E., Kasibante, J., Mpoza, E., Rutakingirwa, M. K, Ssebambulidde, K., Tugume, L., Rhein, J., Boulware, D. R, Mwandumba, H. C, Moyo, M., Mzinganjira, H., Kanyama, C., Hosseinipour, M. C, Chawinga, C., Meintjes, G. A, Schutz, C., Comins, K., Singh, A., Muzoora, C., Jjunju, S., Nuwagira, E., Mosepele, M., Leeme, T., Siamisang, K., Ndhlovu, C. E, Hlupeni, A., Mutata, C., van Widenfelt, E., Chen, T., Wang, D., Hope, W., Boyer-Chammard, T., Loyse, A., Molloy, S. F, Youssouf, N., Lortholary, O., Lalloo, D. G, Jaffar, S., & Harrison, T. S New England Journal of Medicine, 386(12):1109–1120, Massachusetts Medical Society, mar, 2022.

Paper doi abstract bibtex

BACKGROUND Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)– related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS In this phase 3 randomized, controlled, noninferiority trial conducted in five Afri- can countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization–recommended treatment, which includes amphotericin B deoxycho- late (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 partici- pants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal ampho- tericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (differ- ence, −3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P\textless0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was −0.40 log10 colony- forming units (CFU) per milliliter per day in the liposomal amphotericin B group and −0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). CONCLUSIONS Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated crypto- coccal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambi- tion ISRCTN number, ISRCTN72509687.)

@article{Jarvis2022,
abstract = {BACKGROUND Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)– related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS In this phase 3 randomized, controlled, noninferiority trial conducted in five Afri- can countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization–recommended treatment, which includes amphotericin B deoxycho- late (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 partici- pants (24.8{\%}; 95{\%} confidence interval [CI], 20.7 to 29.3) in the liposomal ampho- tericin B group and 117 (28.7{\%}; 95{\%} CI, 24.4 to 33.4) in the control group (differ- ence, −3.9 percentage points); the upper boundary of the one-sided 95{\%} confidence interval was 1.2 percentage points (within the noninferiority margin; P{\textless}0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was −0.40 log10 colony- forming units (CFU) per milliliter per day in the liposomal amphotericin B group and −0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0{\%} vs. 62.3{\%}). CONCLUSIONS Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated crypto- coccal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambi- tion ISRCTN number, ISRCTN72509687.)},
author = {Jarvis, Joseph N and Lawrence, David S and Meya, David B and Kagimu, Enock and Kasibante, John and Mpoza, Edward and Rutakingirwa, Morris K and Ssebambulidde, Kenneth and Tugume, Lillian and Rhein, Joshua and Boulware, David R and Mwandumba, Henry C and Moyo, Melanie and Mzinganjira, Henry and Kanyama, Cecilia and Hosseinipour, Mina C and Chawinga, Chimwemwe and Meintjes, Graeme A and Schutz, Charlotte and Comins, Kyla and Singh, Achita and Muzoora, Conrad and Jjunju, Samuel and Nuwagira, Edwin and Mosepele, Mosepele and Leeme, Tshepo and Siamisang, Keatlaretse and Ndhlovu, Chiratidzo E and Hlupeni, Admire and Mutata, Constantine and van Widenfelt, Erik and Chen, Tao and Wang, Duolao and Hope, William and Boyer-Chammard, Timoth{\'{e}}e and Loyse, Angela and Molloy, S{\'{i}}le F and Youssouf, Nabila and Lortholary, Olivier and Lalloo, David G and Jaffar, Shabbar and Harrison, Thomas S},
doi = {10.1056/NEJMOA2111904},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Jarvis et al. - 2022 - Single-dose liposomal amphotericin B treatment for cryptococcal meningitis.pdf:pdf},
journal = {New England Journal of Medicine},
keywords = {fund{\_}ack,original},
mendeley-tags = {fund{\_}ack,original},
month = {mar},
number = {12},
pages = {1109--1120},
pmid = {35320642},
publisher = {Massachusetts Medical Society},
title = {{Single-dose liposomal amphotericin B treatment for cryptococcal meningitis}},
url = {https://www.nejm.org/doi/full/10.1056/NEJMoa2111904},
volume = {386},
year = {2022}
}

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S"],"bibdata":{"bibtype":"article","type":"article","abstract":"BACKGROUND Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)– related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS In this phase 3 randomized, controlled, noninferiority trial conducted in five Afri- can countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization–recommended treatment, which includes amphotericin B deoxycho- late (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 partici- pants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal ampho- tericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (differ- ence, −3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P\\textless0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was −0.40 log10 colony- forming units (CFU) per milliliter per day in the liposomal amphotericin B group and −0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). CONCLUSIONS Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated crypto- coccal meningitis and was associated with fewer adverse events. 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Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS In this phase 3 randomized, controlled, noninferiority trial conducted in five Afri- can countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization–recommended treatment, which includes amphotericin B deoxycho- late (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 partici- pants (24.8{\\%}; 95{\\%} confidence interval [CI], 20.7 to 29.3) in the liposomal ampho- tericin B group and 117 (28.7{\\%}; 95{\\%} CI, 24.4 to 33.4) in the control group (differ- ence, −3.9 percentage points); the upper boundary of the one-sided 95{\\%} confidence interval was 1.2 percentage points (within the noninferiority margin; P{\\textless}0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was −0.40 log10 colony- forming units (CFU) per milliliter per day in the liposomal amphotericin B group and −0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0{\\%} vs. 62.3{\\%}). 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