NCT03636152

Management of Cardiovascular Disease in Kidney Disease (MaCK) Study

Hydroxychloroquine for the Management of CVD in CKD

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (actual)
• Sponsor: VA Office of Research and Development · Federal
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Cardiovascular disease (CVD) is the largest concerns for patients with Chronic kidney disease (CKD). At present time the investigators do not have proven effective strategies to reduce high CVD related deaths in CKD. This study assesses a novel therapy (hydroxychloroquine, HCQ) for the treatment of CVD in patients with CKD. This is the first human proof-of-concept study and is planned to be conducted among US Veterans, who suffer from both CKD and CVD at a disproportionately greater rates. The outcome of this study has the potential to provide an entirely new line of therapy for the treatment of CVD in CKD.

Detailed description

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, the investigators 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 the investigators through the animal studies validated that HCQ indeed has significant anti-atherosclerosis and vasculoprotective effects in CKD milieu. The investigators further conducted a small, human, feasibility study that shows a potential for HCQ on parameters relevant to CVD in CKD. As the next step, the investigators propose to conduct a proof-of-concept, randomized controlled trial (RCT) to ascertain the effects of HCQ on the structural, functional, and biochemical measures of atherosclerosis and CVD. The investigators will enroll 100 albuminuric, stage 3b CKD subjects in a with 1:1 allocation (HCQ : placebo) and treat for a duration of 18 months. The investigators' three specific aims are as follows: Specific Aim (SA) 1 will evaluate the ability of HCQ, compared to placebo, to slow the progression, or reverse atherosclerosis through serial examination of carotid atherosclerosis through non-contrast MRI performed at baseline and after 9 and 18 months of treatment with HCQ or placebo. The investigators will measure the change in total carotid plaque volume (TPV) as the primary outcome measure, and changes in total plaque surface area, maximal stenosis, and the type (fibrous, stable, or unstable), and stability of plaques as secondary outcome measures. SA2 will evaluate the impact of HCQ vs. placebo on inflammation (SA2a), and vascular stiffness (SA2b) at baseline, and at 6, 9, 12, and 18 months as secondary outcome measures. The investigators will quantify inflammation through high-sensitivity C-reactive protein (SA2a) and vascular stiffness through measurements of aortic pulse wave velocity (SA2b). Specific Aim 3 will examine the effect of HCQ and placebo on the trends of hard cardiac and renal outcomes and drug safety. The results of this trial will provide critical preliminary data to justify and plan a definitive, multicenter RCT to examine the effects of HCQ on hard outcomes of CVD in CKD. Additionally, this study may provide insights into the importance of select inflammatory and vascular factors in CVD with wider future implications for those with CKD and perhaps the general population.

Conditions

• Chronic Kidney Disease
• Cardiovascular Disease
• Inflammation
• Atherosclerosis
• Aortic Stiffness

Interventions

Type	Name	Description
PROCEDURE	MRI carotid	To assess the carotid atherosclerotic plaques
PROCEDURE	APWV	Doppler measurement of the APWV
DRUG	Hydroxychloroquine	Active Drug
DRUG	Matching Placebo	Matching Placebo for the control group.

Timeline

• Start date: 2018-12-14
• Primary completion: 2024-01-31
• Completion: 2024-01-31
• First posted: 2018-08-17
• Last updated: 2025-02-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study