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evident
Original paper
2022NEJMPulmonary/Critical Care

LOVIT

Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit

RCTSepsis

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Overview

In ICU sepsis on vasopressors, IV vitamin C increased death or persistent organ dysfunction at 28 days versus placebo.

Clinical takeaway

LOVIT is a caution against routine intravenous vitamin C in ICU sepsis: the composite of death or persistent organ dysfunction at 28 days was higher than with placebo.

Key result

Death or persistent organ dysfunction at 28 days occurred in 44.5% with vitamin C vs 38.5% with placebo (RR 1.21; 95% CI 1.04-1.40; p=0.01).

Practice impact

Do not use intravenous vitamin C as routine adjunctive therapy for ICU sepsis on vasopressors.

Evidence

Study design

Randomized, placebo-controlled trial.

Enrollment

872

Follow-up

28 days for the primary composite; 6-month survival also reported.

Geography

Not listed

Clinical question

Does intravenous vitamin C reduce death or persistent organ dysfunction at 28 days in ICU adults with sepsis on vasopressors?

Population

  • Adults in the ICU no longer than 24 hours, with proven or suspected infection as the main diagnosis, who were receiving a vasopressor.

Intervention

Intravenous vitamin C 50 mg per kilogram of body weight every 6 hours for up to 96 hours.

Comparator

Matched placebo.

Primary outcome

Composite of death or persistent organ dysfunction (vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28.

Intravenous vitamin C increased the risk of death or persistent organ dysfunction at 28 days compared with placebo.

Risk ratio / 1.21 / 95% CI 1.04-1.40 / p=0.01

Key results

  • Primary composite at 28 days: 44.5% with vitamin C vs 38.5% with placebo; risk ratio 1.21 (95% CI 1.04-1.40; p=0.01).
  • 28-day death: 35.4% vs 31.6% (RR 1.17; 95% CI 0.98-1.40).
  • Persistent organ dysfunction: 9.1% vs 6.9% (RR 1.30; 95% CI 0.83-2.05).
  • Organ-dysfunction scores, biomarkers, 6-month survival, quality of life, stage 3 acute kidney injury, and hypoglycemic episodes were similar.

Harms

  • One patient in the vitamin C group had a severe hypoglycemic episode and another had a serious anaphylaxis event.
  • The primary composite of death or persistent organ dysfunction was higher with vitamin C.

Clinical Use

Practice impact

  • Do not use intravenous vitamin C as routine adjunctive therapy for ICU sepsis on vasopressors.

Applicability

  • Most applicable to adults early in an ICU stay for proven or suspected infection who are already on a vasopressor.

Limitations

  • The intervention was intravenous vitamin C versus matched placebo.
  • Death and persistent organ dysfunction were each directionally higher with vitamin C, but only the composite crossed the primary threshold.

Common misinterpretations

  • LOVIT is not a null trial; the primary outcome was worse with vitamin C.
  • Similar 6-month survival and organ-dysfunction scores do not erase the 28-day composite harm signal.

Related evidence

ProCESS - Same Disease

Citation

Lamontagne F, Masse MH, Menard J, et al. Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit. N Engl J Med. 2022;386(25):2387-2398. doi:10.1056/NEJMoa2200644

In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo.