A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda
Abstract Background While the combination of nifurtimox and eflornithine (NECT) is currently recommended for the treatment of the late stage human African trypansomiasis (HAT), single-agent eflornithine was still the treatment of choice when this trial commenced. This study intended to provide suppo...
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13071-018-2634-x |
| _version_ | 1828450766103248896 |
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| author | Freddie Kansiime Seraphine Adibaku Charles Wamboga Franklin Idi Charles Drago Kato Lawrence Yamuah Michel Vaillant Deborah Kioy Piero Olliaro Enock Matovu |
| author_facet | Freddie Kansiime Seraphine Adibaku Charles Wamboga Franklin Idi Charles Drago Kato Lawrence Yamuah Michel Vaillant Deborah Kioy Piero Olliaro Enock Matovu |
| author_sort | Freddie Kansiime |
| collection | DOAJ |
| description | Abstract Background While the combination of nifurtimox and eflornithine (NECT) is currently recommended for the treatment of the late stage human African trypansomiasis (HAT), single-agent eflornithine was still the treatment of choice when this trial commenced. This study intended to provide supportive evidence to complement previous trials. Methods A multi-centre randomised, open-label, non-inferiority trial was carried out in the Trypanosoma brucei gambiense endemic districts of North-Western Uganda to compare the efficacy and safety of NECT (200 mg/kg eflornithine infusions every 12 h for 7 days and 8 hourly oral nifurtimox at 5 mg/kg for 10 days) to the standard eflornithine regimen (6 hourly at 100 mg/kg for 14 days). The primary endpoint was the cure rate, determined as the proportion of patients alive and without laboratory signs of infection at 18 months post-treatment, with no demonstrated trypanosomes in the cerebrospinal fluid (CSF), blood or lymph node aspirates, and CSF white blood cell count < 20 /μl. The non-inferiority margin was set at 10%. Results One hundred and nine patients were enrolled; all contributed to the intent-to-treat (ITT), modified intent-to-treat (mITT) and safety populations, while 105 constituted the per-protocol population (PP). The cure rate was 90.9% for NECT and 88.9% for eflornithine in the ITT and mITT populations; the same was 90.6 and 88.5%, respectively in the PP population. Non-inferiority was demonstrated for NECT in all populations: differences in cure rates were 0.02 (95% CI: -0.07–0.11) and 0.02 (95% CI: -0.08–0.12) respectively. Two patients died while on treatment (1 in each arm), and 3 more during follow-up in the NECT arm. No difference was found between the two arms for the secondary efficacy and safety parameters. A meta-analysis involving several studies demonstrated non-inferiority of NECT to eflornithine monotherapy. Conclusions These results confirm findings of earlier trials and support implementation of NECT as first-line treatment for late stage T. b. gambiense HAT. The overall risk difference for cure between NECT and eflornithine between this and two previous randomised controlled trials is 0.03 (95% CI: -0.02–0.08). The NECT regimen is simpler, safer, shorter and less expensive than single-agent DFMO. Trial registration ISRCTN ISRCTN03148609 (registered 18 April 2008). |
| first_indexed | 2024-12-10T23:27:51Z |
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| id | doaj.art-33f300c5f0b040eba2e37e2a412bc704 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-12-10T23:27:51Z |
| publishDate | 2018-02-01 |
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| series | Parasites & Vectors |
| spelling | doaj.art-33f300c5f0b040eba2e37e2a412bc7042022-12-22T01:29:30ZengBMCParasites & Vectors1756-33052018-02-0111111110.1186/s13071-018-2634-xA multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in UgandaFreddie Kansiime0Seraphine Adibaku1Charles Wamboga2Franklin Idi3Charles Drago Kato4Lawrence Yamuah5Michel Vaillant6Deborah Kioy7Piero Olliaro8Enock Matovu9Busitema University Faculty of Health SciencesMoyo District Health OfficeMinistry of HealthMoyo HospitalCollege of Veterinary Medicine, Animal Resources & Bio-security, Makerere UniversityArmauer Hansen Research InstituteCompetence Centre in Methodology and Statistics, Luxembourg Institute of HealthGeneva Foundation for Medical Education and ResearchUNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases (TDR)College of Veterinary Medicine, Animal Resources & Bio-security, Makerere UniversityAbstract Background While the combination of nifurtimox and eflornithine (NECT) is currently recommended for the treatment of the late stage human African trypansomiasis (HAT), single-agent eflornithine was still the treatment of choice when this trial commenced. This study intended to provide supportive evidence to complement previous trials. Methods A multi-centre randomised, open-label, non-inferiority trial was carried out in the Trypanosoma brucei gambiense endemic districts of North-Western Uganda to compare the efficacy and safety of NECT (200 mg/kg eflornithine infusions every 12 h for 7 days and 8 hourly oral nifurtimox at 5 mg/kg for 10 days) to the standard eflornithine regimen (6 hourly at 100 mg/kg for 14 days). The primary endpoint was the cure rate, determined as the proportion of patients alive and without laboratory signs of infection at 18 months post-treatment, with no demonstrated trypanosomes in the cerebrospinal fluid (CSF), blood or lymph node aspirates, and CSF white blood cell count < 20 /μl. The non-inferiority margin was set at 10%. Results One hundred and nine patients were enrolled; all contributed to the intent-to-treat (ITT), modified intent-to-treat (mITT) and safety populations, while 105 constituted the per-protocol population (PP). The cure rate was 90.9% for NECT and 88.9% for eflornithine in the ITT and mITT populations; the same was 90.6 and 88.5%, respectively in the PP population. Non-inferiority was demonstrated for NECT in all populations: differences in cure rates were 0.02 (95% CI: -0.07–0.11) and 0.02 (95% CI: -0.08–0.12) respectively. Two patients died while on treatment (1 in each arm), and 3 more during follow-up in the NECT arm. No difference was found between the two arms for the secondary efficacy and safety parameters. A meta-analysis involving several studies demonstrated non-inferiority of NECT to eflornithine monotherapy. Conclusions These results confirm findings of earlier trials and support implementation of NECT as first-line treatment for late stage T. b. gambiense HAT. The overall risk difference for cure between NECT and eflornithine between this and two previous randomised controlled trials is 0.03 (95% CI: -0.02–0.08). The NECT regimen is simpler, safer, shorter and less expensive than single-agent DFMO. Trial registration ISRCTN ISRCTN03148609 (registered 18 April 2008).http://link.springer.com/article/10.1186/s13071-018-2634-xHuman African trypanosomiasis (HAT)Meningo-encephalitic stageSecond-stage HATNifurtimox-eflornithine combination treatment (NECT) |
| spellingShingle | Freddie Kansiime Seraphine Adibaku Charles Wamboga Franklin Idi Charles Drago Kato Lawrence Yamuah Michel Vaillant Deborah Kioy Piero Olliaro Enock Matovu A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda Parasites & Vectors Human African trypanosomiasis (HAT) Meningo-encephalitic stage Second-stage HAT Nifurtimox-eflornithine combination treatment (NECT) |
| title | A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda |
| title_full | A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda |
| title_fullStr | A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda |
| title_full_unstemmed | A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda |
| title_short | A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda |
| title_sort | multicentre randomised non inferiority clinical trial comparing a nifurtimox eflornithine combination to standard eflornithine monotherapy for late stage trypanosoma brucei gambiense human african trypanosomiasis in uganda |
| topic | Human African trypanosomiasis (HAT) Meningo-encephalitic stage Second-stage HAT Nifurtimox-eflornithine combination treatment (NECT) |
| url | http://link.springer.com/article/10.1186/s13071-018-2634-x |
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