A modified Sequential Organ Failure Assessment score for dengue: development, evaluation and proposal for use in clinical trials

Abstract

Background: Dengue is a neglected tropical disease, for which no therapeutic agents have shown clinical efficacy to date. Clinical trials have used strikingly variable clinical endpoints, which hampers reproducibility and comparability of findings. We investigated a delta modified Sequential Organ Failure Assessment (delta mSOFA) score as a uniform composite clinical endpoint for use in clinical trials investigating therapeutics for moderate and severe dengue.

Methods: We developed a modified SOFA score for dengue, measured and evaluated its performance at baseline and 48 h after enrolment in a prospective observational cohort of 124 adults admitted to a tertiary referral hospital in Vietnam with dengue shock. The modified SOFA score included pulse pressure in the cardiovascular component. Binary logistic regression, cox proportional hazard and linear regression models were used to estimate association between mSOFA, delta mSOFA and clinical outcomes.

Results: The analysis included 124 adults with dengue shock. 29 (23.4%) patients required ICU admission for organ support or due to persistent haemodynamic instability: 9/124 (7.3%) required mechanical ventilation, 8/124 (6.5%) required vasopressors, 6/124 (4.8%) required haemofiltration and 5/124 (4.0%) patients died. In univariate analyses, higher baseline and delta (48 h) mSOFA score for dengue were associated with admission to ICU, requirement for organ support and mortality, duration of ICU and hospital admission and IV fluid use.

Conclusions: The baseline and delta mSOFA scores for dengue performed well to discriminate patients with dengue shock by clinical outcomes, including duration of ICU and hospital admission, requirement for organ support and death. We plan to use delta mSOFA as the primary endpoint in an upcoming host-directed therapeutic trial and investigate the performance of this score in other phenotypes of severe dengue in adults and children.

Keywords: Clinical trial endpoint; Delta SOFA; Dengue; Modified SOFA; SOFA; Shock; Vietnam.

Fig. 1

Association between baseline mSOFA score and endpoints. In A, F, G, H and I the probability of having the endpoint is estimated from the binary logistic regression model with a predictor baseline mSOFA score; the blue curve represents the estimated probability and the gray region represents 95% confidence interval. In all plots (A–I), each point represents an individual measurement and is coloured by survivor (red) and non-survivor (blue)

Fig. 2

Association between delta mSOFA score and endpoints. In A, F, G, H and I the probability of having the endpoint is estimated from the binary logistic regression model with a predictor delta mSOFA score; the blue curve represents the estimated probability and the gray region represents 95% confidence interval. In all plots (A–I), each point represents an individual measurement and is coloured by survivor (red) and non-survivor (blue)

Fig. 3

A Distribution of each component of mSOFA score at baseline (red) and day 2 (blue), B Distribution of each component of delta mSOFA score between day 2 and baseline, C Distribution of total mSOFA score (blue) and original SOFA score (red) in all patients

Fig. 4

A-K show the association between each component of mSOFA score and mortality. The probability of having the endpoint is estimated from the binary logistic regression model with a predictor delta mSOFA score; in all panels the blue curve represents the estimated probability and the gray region represents 95% confidence interval. Each point represents an individual measurement and is coloured by survivor (red) and non-survivor (blue). CNS central nervous system; CV cardiovascular