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VOLUME 27 , ISSUE 12 ( December, 2023 ) > List of Articles

Original Article

A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial

Bharath Kumar Tirupakuzhi Vijayaraghavan, Ramesh Venkataraman, Yamunadevi Ramanathan, Saravanan Margabandhu, Devachandran Jayakumar, Pratheema Ramachandran, Neill KJ Adhikari, Francois Lamontagne, Ruxandra Pinto, Marie-Hélène Masse, Julie Ménard, Sheila Sprague, Nagarajan Ramakrishnan

Keywords : Ascorbic acid, Developing countries, Randomized controlled trial, Sepsis

Citation Information : Vijayaraghavan BK, Venkataraman R, Ramanathan Y, Margabandhu S, Jayakumar D, Ramachandran P, Adhikari NK, Lamontagne F, Pinto R, Masse M, Ménard J, Sprague S, Ramakrishnan N. A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial. Indian J Crit Care Med 2023; 27 (12):910-916.

DOI: 10.5005/jp-journals-10071-24587

License: CC BY-NC 4.0

Published Online: 30-11-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Abstract

Background: The burden of sepsis is high in India and is associated with substantial morbidity and mortality. Vitamin C, an endogenous antioxidant, may improve patient outcomes. Methods: This was a parallel-group pilot feasibility randomized controlled trial conducted at 2 intensive care units in India. Adult patients (≥18 years) with proven or suspected infection as the main diagnosis and needing a continuous intravenous vasopressor infusion were randomized to intravenous vitamin C (50 mg/kg every 6 hours for a maximum of 16 doses) or matching placebo. Primary outcomes were related to protocol adherence and feasibility (enrollment per month). The key secondary outcome was the composite of mortality or persistent organ dysfunction (POD) at day 28 after randomization. Results: 60 patients were screened, 51 were eligible, 32 were randomized, and 30 were included in the analysis (randomized/eligible ratio: 0.63). The overall rate of enrollment was 1.5 patients per month. The median (IQR) age was 63.5 (51.0, 70.0) and 70.0% of the patients were male. In both arms, all patients received ≥90% of scheduled doses of the study drug. No patient received open-label vitamin C and there were no deviations from the glucose monitoring protocol. The composite outcome of mortality or POD at day 28 occurred in 56.3% (9/16) in the vitamin C arm as compared to 42.9% (6/14) in the placebo arm [RR: 1.31 (95% CI: 0.62, 2.76), p = 0.47]. Conclusion: In this pilot feasibility randomized controlled trial of vitamin C for adult patients with sepsis, protocol adherence was excellent and feasibility endpoints were met. Trial registration: CTRI/2020/03/024371.


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  1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315(8):801–810. DOI: 10.1001/jama.2016.0287.
  2. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: Analysis for the Global Burden of Study Disease Study. Lancet 2020;395(10219):200–211. DOI: 10.1016/S0140-6736(19)32989-7.
  3. Hammond NE, Kumar A, Kaur P, Tirupakuzhi Vijayaraghavan BK, Ghosh A, Grattan S, et al. Estimates of sepsis prevalence and outcomes in adult patients in the ICU in India: A cross-sectional study. Chest 2022;161(6):1543–1554. DOI: 10.1016/j.chest.2021.12.673.
  4. Divatia JV, Mehta Y, Govil D, Zirpe K, Amin PR, Ramakrishnan N, et al. Intensive Care in India in 2018–2019: The second Indian intensive care case mix and practice patterns study. Indian J Crit Care Med 2021;25(10):1093–1107. DOI: 10.5005/jp-journals-10071-23965.
  5. Marshall JC. Why have clinical trials in sepsis failed? Trends Mol Med 2014;20(4):195–203. DOI: 10.1016/j.molmed.2014.01.007.
  6. Langlois PL, Manzanares W, Adhikari NKJ, Lamontagne F, Stoppe C, Hill A, et al. Vitamin C administration to the critically ill: A systematic review and meta-analysis. JPEN J Parenter Enteral Nutr 2019;43(3):335–346. DOI: 10.1002/jpen.1471.
  7. Fujii T, Salanti G, Belletti A, Bellomo R, Carr A, Furukawa TA, et al. Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: A systematic review and a component network meta-analysis. Intensive Care Med 2022;48(1):16–24. DOI: 10.1007/s00134-021-06558-0.
  8. Agarwal A, Basmaji J, Fernando SM, Zhou Ge F, Xiao Y, Faisal H, et al. Parenteral vitamin C in patients with severe infection: A systematic review. NEJM Evid 2022;1(9). DOI: 10.1056/EVIDoa2200105.
  9. Lamontagne F, Masse MH, Menard J, Sprague S, Pinto R, Heyland DK, et al. Intravenous vitamin C in adults with sepsis in the intensive care unit. N Eng J Med 2022;386:2387–2398. DOI: 10.1056/NEJMoa2200644.
  10. Tirupakuzhi Vijayaraghavan BK, Gupta E, Ramakrishnan N, Beane A, Haniffa R, Lone N, et al. Barriers and facilitators to the conduct of critical care research in low and lower-middle income countries: A scoping review. PLoS One 2022;17(5):e0266836. DOI: 10.1371/journal.pone.0266836.
  11. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2020 statement: Extension to randomized pilot and feasibility trials. BMJ 2016;355:i5239. DOI: 10.1136/bmj.i5239.
  12. Kidney International. KDIGO clinical practice guideline for acute kidney injury. Available from: https://kdigo.org/wp-content/uploads/2016/10/KDIGO-2012-AKI-Guideline-English.pdf (accessed on 26th July 2023).
  13. Cook D, Lauzier F, Rocha MG, Sayles MJ, Finfer S. Serious adverse events in academic critical care research. CMAJ 2008;178(9):1181–1184. DOI: 10.1503/cmaj.071366.
  14. OSF Home. Available from: https://osf.io/xgu5d (accessed on 26 July 2023).
  15. Blaser AR, Alhazzani W, Belley-Cote E, Moller MH, Adhikari NKJA, Burry L, et al. Intravenous vitamin C therapy in adult patients with sepsis: A rapid practice guideline. Acta Anaesthesiol Scand 2023;67(10): 1423–1431. DOI: 10.1111/aas.14311.
  16. Venkataraman R, Divatia JV, Ramakrishnan N, Chawla R, Amin P, Gopal P, et al. Multicenter observational study to evaluate epidemiology and resistance patterns of common intensive care unit-infections. Indian J Crit Care Med 2018;22(1):20–26. DOI: 10.4103/ijccm.IJCCM_394_17.
  17. Bassi A, Arfin S, Joshi R, Bathla N, Hammond NE, Rajbhandari D, et al. Challenges in operationalising clinical trials in India during the COVID-19 pandemic. Lancet Glob Health 2022;10(3):e317–e319. DOI: 10.1016/S2214-109X(21)00546-5.
  18. Tirupakuzhi Vijayaraghavan BK, Jha V, Rajbhandari D, Myatra SN, Ghosh A, Bhattacharya A, et al. Hydroxychloroquine plus personal protective equipment versus personal protective equipment alone for the prevention of laboratory-confirmed COVID-19 infections among healthcare workers: A multicentre, parallel-group randomised controlled trial from India. BMJ Open 2022;12(6):e059540. DOI: 10.1136/bmjopen-2021-059540.
  19. Munch MW, Myatra SN, Tirupakuzhi Vijayaraghavan BK, Saseedharan S, Benfield T, Wahlin RR, et al. Effect of 12mg vs 6mg of dexamethasone on the number of days alive without life support in adults with COVID-19 and severe hypoxemia: The COVID STEROID 2 randomized trial. JAMA 2021;326(18):1807–1817. DOI: 10.1001/jama.2021.18295.
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