# Hydroxychloroquine for the Management of CVD in CKD

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

Cardiovascular disease (CVD) is the most prominent cause of morbidity and mortality among patients with
chronic kidney disease (CKD), and end stage kidney disease (ESKD). Unfortunately at the present time, we do
not have an effective treatment to reduce the high CVD mortality in these populations. Accelerated
atherosclerosis, inflammation, and vascular stiffness are prominent factors contributing to CVD in CKD.
Interventions that can effectively counter these factors may provide significant benefits for the management of
CVD in CKD. Hydroxychloroquine (HCQ) is an inexpensive and safe anti-inflammatory drug that has been in
clinical use for over 4 decades even in patients with CKD and ESKD. In recent times, multiple in vitro, in vivo,
and human cohort based data have shown that HCQ benefits multiple parameters of CVD, including
inflammation, endothelial function, metabolic syndrome, insulin sensitivity and atherosclerosis. Recently we
through our animal validated that HCQ indeed has significant anti-atherosclerosis and vasculoprotective effects
in CKD milieu. We further conducted a small, human, feasibility study that shows a potential for HCQ on
parameters relevant to CVD in CKD.
 The next step requires evaluation of HCQ's role for the treatment of CVD in CKD. However, in the absence
of a universally agreed-on surrogate for CVD, a proof-of-concept clinical study needed to validate the anti-
atherosclerosis and vasculoprotective potential of HCQ in CKD. We propose such a study that will enroll 90
albuminuric, stage 3b CKD subjects in a randomized controlled trial (RCT) with 1:1 allocation (HCQ : placebo),
stratified by their diabetes status, and treat for a duration of 18 months. We will examine the effects of HCQ on
structural, functional, and biochemical measures of atherosclerosis and CVD.
Specific Aim (SA) 1 will evaluate the ability of HCQ, compared to placebo, to slow the progression, or reverse
atherosclerosis. We will evaluate the progression of carotid atherosclerosis with a non-contrast MRI performed
at baseline and after 9 and 18 months of treatment with HCQ or placebo. The primary outcome measure will
be change in total carotid plaque volume (TPV). Secondary outcome measures will be changes over time in
total plaque surface area, maximal stenosis, and the type (fibrous, stable, or unstable), and stability of plaques.
Specific Aim 2: will evaluate the extent to which HCQ can affect inflammation (SA2a), and vascular stiffness
(SA2b) in CKD. We will examine the effects of HCQ and placebo at baseline, and at 6, 9, 12, and 18 months
on the secondary outcome measures of high-sensitivity C-reactive protein (SA2a) and aortic pulse wave
velocity (SA2b).
 Though the sample size and power calculations have been designed for the primary outcome (SA1), we
will have adequate power to evaluate meaningful impacts of HCQ on the secondary outcomes in SA2.
Specific Aim 3 will examine the effect of HCQ and placebo on the trends of hard cardiac and renal o...

## Key facts

- **NIH application ID:** 10038795
- **Project number:** 5I01CX001661-03
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** MARK S. SEGAL
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038795

## Citation

> US National Institutes of Health, RePORTER application 10038795, Hydroxychloroquine for the Management of CVD in CKD (5I01CX001661-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10038795. Licensed CC0.

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