Ubiquinol (reduced Coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled, pilot trial

Michael W Donnino, Sharri J Mortensen, Lars W Andersen, Maureen Chase, Katherine M Berg, Julia Balkema, Jeejabai Radhakrishnan, Raúl J Gazmuri, Xiaowen Liu, Michael N Cocchi, Michael W Donnino, Sharri J Mortensen, Lars W Andersen, Maureen Chase, Katherine M Berg, Julia Balkema, Jeejabai Radhakrishnan, Raúl J Gazmuri, Xiaowen Liu, Michael N Cocchi

Abstract

Introduction: We previously found decreased levels of Coenzyme Q10 (CoQ10) in patients with septic shock. The objective of the current study was to assess whether the provision of exogenous ubiquinol (the reduced form of CoQ10) could increase plasma CoQ10 levels and improve mitochondrial function.

Methods: We performed a randomized, double-blind, pilot trial at a single, tertiary care hospital. Adults (age ≥18 years) with severe sepsis or septic shock between November 2012 and January 2014 were included. Patients received 200 mg enteral ubiquinol or placebo twice a day for up to seven days. Blood draws were obtained at baseline (0 h), 12, 24, 48, and 72 h. The primary outcome of the study was change in plasma CoQ10 parameters (total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10). Secondary outcomes included assessment of: 1) vascular endothelial biomarkers, 2) inflammatory biomarkers, 3) biomarkers related to mitochondrial injury including cytochrome c levels, and 4) clinical outcomes. CoQ10 levels and biomarkers were compared between groups using repeated measures models.

Results: We enrolled 38 patients: 19 in the CoQ10 group and 19 in the placebo group. The mean patient age was 62 ± 16 years and 47% were female. Baseline characteristics and CoQ10 levels were similar for both groups. There was a significant increase in total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10 in the ubiquinol group compared to the placebo group. We found no difference between the two groups in any of the secondary outcomes.

Conclusions: In this pilot trial we showed that plasma CoQ10 levels could be increased in patients with severe sepsis or septic shock, with the administration of oral ubiquinol. Further research is needed to address whether ubiquinol administration can result in improved clinical outcomes in this patient population.

Trial registration: Clinicaltrials.gov identifier NCT01948063. Registered on 18 February 2013.

Figures

Fig. 1
Fig. 1
Consolidated Standards for Reporting Trials (CONSORT) diagram. A total of 546 patients were screened. Of these 41 were randomized and 38 were analyzed. CMO: Comfort measures only, DNI: Do Not Intubate, DNR: Do Not Resuscitate NPO: nil per os
Fig. 2
Fig. 2
CoQ10 parameters over time. Values are reported as medians with errors bars indicating first and third quartiles. The P values represent the global tests that values are similar between groups at the 12 and 24 h time points
Fig. 3
Fig. 3
Vascular and inflammatory biomarkers over time. Values are reported as log-transformed means with errors bars indicating standard deviations. The P values represent the global tests that values are similar between groups at the 12, 24, 48, and 72 h time points
Fig. 4
Fig. 4
Cytochrome c values over time. Values are reported as log-transformed means with errors bars indicating standard deviations. The P values represent the global tests that values are similar between groups at the 12 and 24 h time points
Fig. 5
Fig. 5
Cell-free DNA, and nucleus and mitochondrial DNA values over time. Values are reported as log-transformed means with errors bars indicating standard deviations. The P values represent the global tests with values that are similar between groups at the 12 and 24 h time points

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