Hydroxychloroquine in Cardiovascular Disease in Patients With Chronic Kidney Disease: A Proof of Concept Study

NCT01537315 | Terminated Phase 2 Results DMC

• 1 other identifier: 132036
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

Presence of multiple traditional and nontraditional risk factors of atherosclerosis and cardiovascular disease (CVD) including inflammation in patients with chronic kidney disease (CKD) contribute to high CVD morbidity and mortality in this patient population. Additionally, the traditional approaches towards the therapy of CVD have little impact on CV mortality in these patients. Hydroxychloroquine (HCQ) used as anti-inflammatory in rheumatological disorders, has multiple beneficial properties relevant to the process of vascular disease. The effects of HCQ on atherosclerosis (AS) and vascular disease in CKD is not known yet. Thus, the study hypothesis is that HCQ treatment in individuals with CKD will provide clinically significant benefit in the management of CVD and will provide biological and functional atherosclerotic benefits.

Conditions

Kidney Failure, Chronic; Cardiovascular Disease; Arteriosclerosis

Keywords

Kidney Failure, Chronic; Cardiovascular Disease; Arteriosclerosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Inflammatory Marker, Hs-C Reactive Protein, at 6 Months

  Hs-CRP will be measured at baseline (before study drug) and at end of study (6 months). This marker is measured by ELISA assay from serum.

  Baseline and 6 months

Study Arms (2)

Matching Placebo

PLACEBO COMPARATOR

Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) will be randomized to either hydroxychloroquine (HCQ) or matching placebo in a 3:1 ratio (approximately 39 to HCQ and 13 to placebo)

Other: Matching Placebo

Hydroxychloroquine

EXPERIMENTAL

Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) will be randomized to either hydroxychloroquine (HCQ) or matching placebo in a 3:1 ratio (approximately 39 to HCQ and 13 to placebo)

Drug: Hydroxychloroquine

Interventions

Hydroxychloroquine DRUG

200 mg capsule daily for 10 +/- 4 days, then 200 mg twice daily till end of study (duration approximately 6 months)

Also known as: Plaquenil

Hydroxychloroquine

Matching Placebo OTHER

matching placebo capsule 200 mg daily for 10 +/- 4 days and thereafter 200 mg twice a day for duration of study, approximately 6 months

Matching Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measured stage IV proteinuric chronic kidney disease with an estimated Modification of Diet in Renal Disease (MDRD) GFR (eGFR) of 18 to 35 ml/min.
• Current or history of documented proteinuria of more than or equal to 300 mg/dL in 24 hours or a spot urine protein to creatinine ratio of greater than 0.3 ug/mg.
• Not on dialysis.
• Ages 18 to 80 years, both sexes, all races and ethnicities

You may not qualify if:

• glucose-6-phosphate dehydrogenase (G6PD) deficiency or known hypersensitivity to 4-aminoquinoline compounds (such as chloroquine or hydroxychloroquine).
• Abnormal liver functions; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) more than 2.5 times the normal or international normalized ratio (INR) without being anti-coagulated greater than 1.4.
• Known chronic active infections like HIV, Hepatitis B or Hepatitis C positive, chronic osteomyelitis etc.
• Recent serious infection including Pneumonia requiring hospitalization, meningitis, septicemia in the 2 months prior to screening.
• Active or recently treated (\< 1 year in remission) malignancy or systemic inflammatory diseases (Patients with localized squamous cell carcinoma of the skin are eligible).
• Pregnancy, breastfeeding or planning to become pregnant during the course of the study.
• Use of systemic corticosteroids or other immunosuppression within last 3 months (acute course of steroid for a gouty arthritis or chronic obstructive pulmonary disease (COPD) is eligible if \> 1 month ago).
• History of prolonged corrected QT interval \> 450.
• Inability to attend or comply with treatment or follow-up scheduling.
• Life expectancy less than 6 months or uncontrolled congestive heart failure (CHF) (defined as more than 2 admissions in prior 6 months).
• Any other condition the PI determines may put the research subject in jeopardy during the course of the study.

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (3)

Central Arkansas Veterans Healthcare System

Little Rock, Arkansas, 72205, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of Florida

Gainesville, Florida, 32610-0224, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic; Cardiovascular Diseases; Arteriosclerosis

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dumitru Rotaru, MD, PI
• Organization: University of Arkansas for Medical Sciences

drotaru@uams.edu

501/526-6919

Study Officials

• Dumitru Rotaru, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: February 23, 2012
• Study Start: February 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: November 19, 2014
• Results First Posted: November 19, 2014

Record last verified: 2014-11

Locations

US (3)