CHICAGO — A novel anti-inflammatory compound failed to curb renal dysfunction induced by exposure to contrast agents in the CARIN trial.
Four days after percutaneous coronary intervention (PCI), contrast nephropathy — signaled by an absolute increase of 0.3 mg/dL from baseline serum creatinine and decrease in urine output — was not reduced in patients receiving CMX-2043, no matter the dosage (P>0.1), Deepak L. Bhatt, MD, MPH, of Boston’s Brigham and Women’s Hospital, reported at the American College of Cardiology (ACC) 2016 Scientific Sessions.
As CMX-2043 joins “the graveyard of compounds that don’t work,” Bhatt concluded that “there remains an unmet clinical need to find agents that reduce the occurrence of contrast nephropathy.”
C. Michael Valentine, MD, of Stroobants Cardiovascular Center in Lynchburg, Va., agreed that CARIN is only the latest failure in the pursuit of such a kidney protective agent. “We continue to find that saline and the limitation of contrast agents are really the only things that help us,” he said at a press conference.
“When patients come in with heart attacks, we’re in a double bind trying to save their kidneys while helping their hearts,” Valentine added, because many patients have concomitant kidney and heart disease.
The double-blinded CARIN study included 361 patients randomized to different doses of the compound or placebo.
Major adverse cardiovascular or kidney events showed no difference between CMX-2043 recipients and the control group at 90 days (P>0.1). Death, cardiovascular death, and dialysis also occurred at similar rates between groups (P>0.1).
Bhatt noted that CMX-2043 had shown potential for protection against acute kidney injury in earlier studies. For example, the SUPPORT-1 trial included 142 drug recipients who exhibited a reduction in creatine kinase and cardiac troponin T with no drug-related serious adverse events.
Despite the negative findings of the present investigation, he said, “the CARIN trial design may serve as a template to efficiently determine whether agents that appear promising in pre-clinical studies are worth taking into larger, more expensive phase III evaluations.”
The CARIN trial was funded by Ischemix.
Bhatt cited relationships with Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Boston VA Research Institute, Society of Cardiovascular Patient Care, American Heart Association, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute, American College of Cardiology, Belvoir Publications, HMP Communications, Journal of the American College of Cardiology, Slack Publications, Society of Cardiovascular Patient Care, WebMD, Clinical Cardiology, NCDR-ACTION Registry Steering Committee, VA CART Research and Publications Committee, Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company; Elsevier, Biotronik, Boston Scientific, St. Jude Medical, FlowCo, PLx Pharma, Takeda.
American College of Cardiology
Bhatt DL, et al “A prospective, comparative, randomized, multi-center, double-blinded, placebo-controlled, phase 2a study of the safety and efficacy of CMX-2043 for periprocedural injury protection in subjects undergoing coronary angiography at risk of radio-contrast induced nephropathy” ACC 2016.