Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) Trial

Beth Israel Lahey Health

Status and phase: Completed; Phase 3; Phase 2

Conditions: Metabolic Disturbance; Septic Shock; Sepsis

Treatments: Drug: vitamin C, vitamin B1, hydrocortisone; Drug: Normal saline

Study type: Interventional

Funder types: Other

Identifiers

NCT03389555

2017P000436

Details and patient eligibility

About

In this study, we aim to determine whether the combination of Ascorbic Acid (Vitamin C), Thiamine (Vitamin B1), and Corticosteroids improves the trajectory of organ failure and reduces mortality in patients with sepsis and septic shock as compared to placebo.

Full description

Sepsis and Septic Shock are common and highly morbid clinical conditions without any specific therapy aside from antibiotics. A recent quasi-experimental study (Marik et. al., PMID 27940189) demonstrated a remarkable benefit when the combination of Ascorbic Acid (Vitamin C), Corticosteroids, and Thiamine (Vitamin B1) were given to patients with sepsis. In particular, patients who received this combination of medications required a shorter amount of time on vasopressors, suffered less organ failure, and had improved mortality. Vitamin C has long been suggested for treatment of patients with severe infection as it exerts significant anti-oxidant effects and reduces endothelial permeability. Corticosteroids, a mainstay of therapy for refractory shock in sepsis, have also been shown to enhance the beneficial cellular effects of vitamin C. Finally, thiamine has been shown to be an effective mitochondrial resuscitator in sepsis, especially for the ~30% of septic shock patients who present with thiamine deficiency (Donnino et. al, PMID 26771781).

In this study, we aim to reproduce the findings of Marik et. al. using a more rigorous study design (i.e. a blinded, randomized clinical trial) and focus on the important clinical outcomes of organ failure and death.

Enrollment: 205 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Adult patient (age ≥ 18 years)
2. Suspected (cultures drawn and antibiotic given) or confirmed (via culture results) infection
3. Receiving vasopressor (norepinephrine, phenylephrine, epinephrine, dopamine, angiotensin II or vasopressin)

Exclusion criteria

1. Member of a protected population (pregnant, prisoner)
2. Known kidney stones within the past 1 year (except for asymptomatic, incidentally noted stones on imaging)
3. End stage renal disease (ESRD) requiring dialysis
4. Known Glucose-6-Phosphate Dehydrogenase deficiency
5. Known Hemachromatosis
6. Comfort Measures Only status
7. Anticipated death within 24-hours despite maximal therapy (as determined by the enrolling physician)
8. Receiving supplemental thiamine in a dose greater than that contained in a multivitamin
9. Clinical indication for steroids (e.g. chronic use) as determined by the clinical team providing this drug
10. Clinical indication for thiamine as determined by the clinical team providing this drug
11. Clinical indication for ascorbic acid as determined by the clinical team providing this drug
12. Known allergy to vitamin C, hydrocortisone, or thiamine

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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205 participants in 2 patient groups, including a placebo group

Vitamin C, Vitamin B1, Corticosteroids

Experimental group

Description:

The combination of vitamin C, vitamin B1, hydrocortisone : * Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days * Vitamin B1 (thiamine) 100mg every 6 hours x 4-days * Hydrocortisone 50mg every 6 hours x 4-days

Treatment:

Drug: vitamin C, vitamin B1, hydrocortisone

Placebo

Placebo Comparator group

Description:

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Treatment:

Drug: Normal saline