Table 2.
Interventions for which a clinical trial has been proposed during the present outbreak
|
Present knowledge |
Potential issues for large-scale use in Africa | |||
|---|---|---|---|---|
| Mechanism of action | Safety | Efficacy | ||
| Amiodarone | Inhibition of viral entry | Widespread human use for more than 30 years; toxic effects are mainly reported for long-lasting use; potential acute toxic effects in case of low potassium concentrations in blood | In-vitro data show significant suppression of viral replication and infectivity at the same plasma concentration reached for clinical management of arrhythmia;9 unpublished data on case-by-case use has not provided clear evidence for or against efficacy so far | No available in-vivo evidence for efficacy; however, the drug is easy to administer (available in both intravenous and oral routes, and is thermostable); the drug is low cost and already available for large-scale use |
| ZMapp | Neutralising antibody | Data on human beings are very restricted | 100% efficacy on NHP;10 case-by-case experiences on human beings are very restricted but promising11 | Difficult to administer, potentially very expensive, and no guarantee exists that production can be scaled for wide use |
| Brincidofovir | Unclear | Tested in a clinical trial for DNA viruses; generally better tolerated than the already approved cidofovir12 | Unpublished data from Viral Special Pathogens Branch (USA) revealed that in-vitro activity of brincidofovir against the Ebola virus is similar to that reported against other viral diseases; no animal data;13 was used on two occasions in human beings with Ebola virus disease (one died and one survived) | The manufacturer has recently decided to stop experimentation in human beings |
| ECP | Neutralising antibody | Mainly transfusion related | Whole blood and ECP have been already used as empirical treatments with promising results in a small group of cases of Ebola virus disease12, 14, 15 | WHO has already developed a guidance for use of ECP;15 potential limitations are related to availability and risk for transmission of infections other than Ebola virus disease |
| QBD + XBJ | Immunomodulators16, 17 | Not assessed according to stringent regulatory authority requirements; however, human use is presumed to be widespread in China; both drugs are sold online | No available data on patients with Ebola virus disease | .. |
| Favipiravir | Inhibitor of viral RNA-dependent RNA polymerase | Well tolerated in patients without Ebola virus disease; evidence from large clinical trials; the drug is approved for human use in Japan at present; preliminary data exist on patients with Ebola virus disease18 | Evidence from studies in vitro and in small animals for activity against Zaire ebolavirus;19 preliminary data on human use (case-by-case use and early analysis of trials) has not provided evidence on efficacy so far | Favipiravir is conveniently formulated in oral thermostable tablets, but cost might be high as it is a patented drug; Toyama Chemical announced in October, 2014, that it had 20 000 courses of treatment in stock |
| TKM-Ebola | Cleaves Ebola RNA inside the cell | Increased cytokines in safety studies on human beings;12 FDA suspended phase 1 in July, 2014; in August, 2014, the FDA changed the status to partial hold, allowing the drug to be used under expanded access in people infected with Ebola virus but with the phase 1 trial still suspended (NCT02041715) | Up to 100% efficacy in NHP12 | Potentially very expensive and no guarantee exists that production for wide use can be scaled |
NHP=non-human primates. ECP=Ebola convalescent plasma. QBD=Qingwenbaidu decoction (herbal product). XBJ=Xuebijing injection (herbal product). FDA=US Food and Drug Administration.