Key recommendations for a trial implementation in an Ebola outbreak.

<p>Key recommendations for a trial implementation in an Ebola outbreak.</p

JIKI trial: correlation between EBOV RT-PCR Ct value and RNA viral load at baseline in adolescents and adults.

<p>The black line represents the regression line. The Spearman rank correlation coefficient was 0.88 (<i>p</i> < 0.001). A baseline Ct value of 20 corresponded to an RNA viral load of 5 × 10⁷ genome copies/ml of plasma (7.7 log₁₀ copies/ml). Of the 99 adolescents and adults, 84 had both an RT-PCR Ct and an RNA viral load measurement at baseline. Red dots represent patients who died. Blue dots represent patients who survived.</p

JIKI trial mortality, according to age and baseline RT-PCR Ct value.

<p>Histograms represent mortality percentages. Vertical bars represent 95% confidence intervals. Red bars represent target values. The RT-PCR assay was conducted using the RealStar Filovirus Screen RT-PCR Kit 1.0 (Altona Diagnostics).</p

JIKI trial: evolution of RT-PCR Ct values and RNA viral load in adolescents and adults.

<p>(A) Evolution of RT-PCR Ct values. (B) Evolution of RNA viral loads. The <i>x</i>-axis represents the time since first symptoms (for example, for a patient whose first symptom occurred 5 d before admission to the treatment center, the baseline value dot is positioned at 5 d). Each line represents one patient. Dots represent baseline values, X’s represent follow-up values, and asterisks represent values below the limit of quantification. Red symbols represent patients who died; blue symbols represent patients who survived.</p

JIKI trial: evolution of RNA viral load in adolescents and adults.

<p>(A) Evolution of RNA viral load in adolescents and adults who survived. The <i>x</i>-axis represents the time since favipiravir initiation (day 0). Each blue line represents one patient (<i>n</i> = 48). Circles represent baseline and follow-up values. Asterisks represent values under the limit of detection (3.4 log₁₀ copies/ml). The black line represents the mean log₁₀ viral load decline estimated from a linear mixed effect model. The mean initial viral load was estimated at 6.65 log₁₀ copies/ml (SD 0.86), and the mean slope of viral load evolution at −0.33 log₁₀ copies/ml (SD 0.03) per day of follow-up. (B) Evolution of RNA viral load in adolescents and adults who died. The <i>x</i>-axis represents the time since favipiravir initiation (day 0). Each red line represents one patient (<i>n</i> = 49). Circles represent baseline and follow-up values. The black line represents the mean log₁₀ viral load evolution estimated from a linear mixed effect model. The mean initial viral load was estimated at 8.54 log₁₀ copies/ml (SD 0.21), and the mean slope of viral load evolution at −0.001 log₁₀ copies/ml (SD 0.15) per day of follow-up.</p

JIKI trial: participants’ characteristics, according to age and baseline Ct value.

<p>JIKI trial: participants’ characteristics, according to age and baseline Ct value.</p

JIKI trial: evolution of serum creatinine, aspartate aminotransferase, alanine aminotransferase, and creatine phosphokinase in adolescents and adults.

<p>The <i>x</i>-axis represents the time since first symptoms (for example, for a patient whose first symptom occurred 5 d before day 0, the baseline value dot is positioned at 5 d). Each line represents one patient. Dots represent baseline values, and X’s represent follow-up values. Red symbols represent patients who died; blue symbols represent patients who survived. Dark red lines represent patients with baseline Ct < 20 who died, light red lines represent patients with baseline Ct ≥ 20 who died, dark blue lines represent patients with baseline Ct < 20 who survived, and light blue lines represent patients with baseline Ct ≥ 20 who survived. Samples obtained more than 25 d after onset of symptoms are not represented.</p

JIKI trial: evolution of serum creatinine, transaminases, and creatine phosphokinase in the 11 adolescents and adults who had worsening in at least one biochemical parameter on favipiravir.

<p>(A) Patients who survived (<i>n</i> = 7). (B) Patients who died (<i>n</i> = 4). Each line represents one patient. All patients are identified with an ID number (from 1 to 7) or letter (from a to d) throughout the figures. For all 11 patients, all available data are shown. Dots represent baseline values, and X’s represent follow-up values. Dark blue lines represent patients with baseline Ct < 20 who survived. Light blue lines represent patients with baseline Ct ≥ 20 who survived. Light red lines represent patients with baseline Ct ≥ 20 who died. The <i>x</i>-axis represents the time since first symptoms (for example, for a patient whose first symptom occurred 5 d before admission to the treatment center, the baseline value dot is positioned at 5 d). Samples obtained more than 25 d after onset of symptoms are not represented. All 11 patients continued favipiravir.</p

JIKI trial progress.

<p>ALIMA, Alliance for International Medical Action; CRF, Croix Rouge Française (French Red Cross); EU, European Union; Inserm, Institut National de la Santé et de la Recherche Médicale; SSA, Service de Santé des Armées (French military health service).</p

JIKI trial: baseline serum creatinine in adolescents and adults and outcomes according to baseline values.

<p>Creat, creatinine.</p