
==== Front
Indian J Crit Care Med
Indian J Crit Care Med
IJCCM
Indian Journal of Critical Care Medicine : Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine
0972-5229
1998-359X
Jaypee Brothers Medical Publishers

38477008
10.5005/jp-journals-10071-24654
Letter to the Editor
Author Response
Vijayaraghavan Bharath Kumar Tirupakuzhi 1https://orcid.org/0000-0002-1801-0667

Venkataraman Ramesh 2https://orcid.org/0000-0003-1949-3979

Ramakrishnan Nagarajan 3https://orcid.org/0000-0001-5208-4013

1 Department of Critical Care Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India
2,3 Department of Critical Care, Apollo Hospitals, Chennai, Tamil Nadu, India
Bharath Kumar Tirupakuzhi Vijayaraghavan, Department of Critical Care Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India, Phone: +91 9043330655, e-mail: bharath@icuconsultants.com
3 2024
29 2 2024
28 3 312312
Copyright © 2024; The Author(s).
2024
https://creativecommons.org/licenses/by-nc/4.0/ © The Author(s). 2024 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
How to cite this article

Tirupakuzhi Vijayaraghavan BK, Venkataraman R, Ramakrishnan N. Author Response. Indian J Crit Care Med 2024;28(3):312.

Keywords

Randomized controlled trial
Sepsis
Vitamin C
==== Body
pmc Dear Editor,

We thank Dr Angadi and colleagues for their interest in our pilot trial and for engaging in this discussion.

At the outset, we need to clarify that our trial is a small pilot randomized controlled trial with the key and stated aim of demonstrating feasibility. While we reported secondary outcomes, as stated in our manuscript, they are to be considered exploratory. We respond below to each of their comments.

In a randomized controlled trial, any imbalances in baseline characteristics are by definition a product of chance. Current recommendations are to report them as they stand by the intervention arm and not perform any inferential testing.1 In a large trial, it would be expected that baseline characteristics balance out between the arms. In a small trial like ours, some imbalances are only natural. As can be seen from Table 1 of our trial, median APACHE II was higher in the placebo arm whereas median SOFA was higher in the vitamin C arm. We did not adjust for these imbalances in our analysis of secondary outcomes as our trial was primarily designed to demonstrate feasibility. Differences noted in secondary outcomes as stated above are to be considered exploratory. We would also like to draw the attention of the authors to the larger and definitive parent LOVIT trial which was published in June 2022 and demonstrated a signal of harm from intravenous vitamin C.2

Regarding any confounding from the use of corticosteroids, again the very nature of a randomized controlled trial ensures that known and unknown confounders are balanced between arms. In our trial, a slightly lower proportion of patients in the vitamin C arm received corticosteroids on day 1 (56.3%) as compared to the placebo arm (64.3%). We would not read too much into these differences or their impact on clinical outcomes as this was a small feasibility trial. In the parent LOVIT trial, there was no difference in the use of steroids between arms and as already stated above, the trial demonstrated a signal of harm from intravenous vitamin C.2

Regarding additional outcomes and serum levels of vitamin C, our goals were to demonstrate feasibility, and as such, these were beyond the remit of our trial. The larger LOVIT trial did measure vitamin C levels and also performed a subgroup analysis which did not show any differential effect of the vitamin based on levels.2

We once again thank the authors for engaging with our study.

Orcid

Bharath Kumar Tirupakuzhi Vijayaraghavan https://orcid.org/0000-0002-1801-0667

Ramesh Venkataraman https://orcid.org/0000-0003-1949-3979

Nagarajan Ramakrishnan https://orcid.org/0000-0001-5208-4013

Source of support: Nil

Conflict of interest: None
==== Refs
References

1. Knol MJ Groenwold RHH Grobbee DE P values in baselines tables of randomized controlled trials are inappropriate, but still common in high impact journals Eur J Prev Cardiol 2012 19 2 231 232 10.1177/1741826711421688 22512015
2. 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 10.1056/NEJMoa2200644
