Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial
Clinical Infectious Diseases February 15, 2016 V.62 N.4 P.468-476
James Whitehorn, Chau Van Vinh Nguyen, Lam Phung Khanh, Duong Thi Hue Kien, Nguyen Than Ha Quyen, Nguyen Thi Thanh Tran, Nguyen Thuy Hang, Nguyen Thanh Truong, Luong Thi Hue Tai, Nguyen Thi Cam Huong, Vo Thanh Nhon, Ta Van Tram, Jeremy Farrar, Marcel Wolbers, Cameron P. Simmons, and Bridget Wills
1London School of Hygiene and Tropical Medicine, United Kingdom
2Oxford University Clinical Research Unit
3Hospital for Tropical Diseases, Ho Chi Minh City
4Tien Giang Hospital, My Tho, Vietnam
5Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom
6Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Victoria, Australia
Dengue is a viral disease for which there is currently no therapeutic agent. We investigated the potential of lovastatin in the treatment of dengue. Lovastatin was safe and well tolerated, but did not demonstrate a therapeutic benefit.
Dengue endangers billions of people in the tropical world, yet no therapeutic is currently available. In part, the severe manifestations of dengue reflect inflammatory processes affecting the vascular endothelium. In addition to lipid lowering, statins have pleiotropic effects that improve endothelial function, and epidemiological studies suggest that outcomes from a range of acute inflammatory syndromes are improved in patients already on statin therapy.
Following satisfactory review of a short pilot phase (40 mg lovastatin vs placebo in 30 cases), we performed a randomized, double-blind, placebo-controlled trial of 5 days of 80 mg lovastatin vs placebo in 300 Vietnamese adults with a positive dengue NS1 rapid test presenting within 72 hours of fever onset. The primary outcome was safety. Secondary outcomes included comparisons of disease progression rates, fever clearance times, and measures of plasma viremia and quality of life between the treatment arms.
Adverse events occurred with similar frequency in both groups (97/151 [64%] placebo vs 82/149 [55%] lovastatin; P = .13), and were in keeping with the characteristic clinical and laboratory features of acute dengue. We also observed no difference in serious adverse events or any of the secondary outcome measures.
We found lovastatin to be safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, we found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. Continuing established statin therapy in patients who develop dengue is safe.
Chinese Clinical Trials Registration.ISRCTN03147572.
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