BTG plc (LSE: BTG), the global healthcare company, today announced the start of a randomized double-blinded clinical study, initiated by researchers at the University of Maryland School of Medicine (UMSOM), that examines the role of DigiFab® (Digoxin Immune FAB (ovine)) in patients with an elevated risk of acute kidney injury undergoing coronary artery bypass graft (CABG) surgery.
Acute kidney injury (AKI) occurs in nearly 30 percent of patients undergoing CABG surgeryi, and AKI often requires patients to undergo dialysis. More than 200,000 CABG procedures are carried out in the US annuallyii. In patients needing dialysis, the risk of death is very high. There are no known therapies that reduce the chance of developing kidney damage after heart surgery. There is evidenceiii that patients with high levels of a substance called endogenous ouabain may have an increased risk of developing kidney damage.
The UMSOM researchers hypothesize that DigiFab® could prevent kidney injury by binding to ouabainiv, v. This study examines whether providing DigiFab® will reduce ouabain levels and lower the risk of developing kidney damage after heart surgery.
In the trial, 250 patients who are scheduled to undergo CABG procedures at University of Maryland Medical Center and University of Maryland St Joseph Medical Center will be screened, enrolled and randomized to treatment with either DigiFab® or placebo. The study involves a follow up period after CABG surgery to evaluate renal function and the need for dialysis.
The study, which enrolled its first patient in July, is titled Preop Digifab in CABG to Reduce Ouabain Levels and Prevent AKI. Primary completion is expected in 2021.
DigiFab® is currently indicated in the US for the treatment of patients with life-threatening or potentially life-threatening toxicity or overdose of the drug digoxin, which is used to treat heart failure. This includes known suicidal or accidental consumption of fatal doses of digoxin. It also includes chronic ingestions causing toxic steady-state serum digoxin concentrations, as well as manifestations of life-threatening toxicity of digoxin overdose such as severe ventricular arrhythmias, progressive bradycardia, and second or third degree heart block not responsive to atropine, and serum potassium levels exceeding safe levels with rapidly progressive signs and symptoms of digoxin toxicity.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Known suicidal or accidental consumption of fatal doses of digoxin: 10 mg or more of digoxin in healthy adults, or 4 mg (or more than 0.1 mg/kg) in healthy children, or ingestion of an amount that can cause steady state serum concentrations of ≥10 ng/mL; Chronic ingestions causing steady-state serum digoxin concentrations >6 ng/mL in adults or 4 ng/mL in children; Manifestations of life-threatening toxicity of digoxin overdose such as severe ventricular arrhythmias, progressive bradycardia, and second or third degree heart block not responsive to atropine, serum potassium levels exceeding 5.5 mEq/L in adults or 6 mEq/L in children with rapidly progressive signs and symptoms of digoxin toxicity.
General: Suicidal ingestion may result from more than one drug. Consider toxic effects of other drugs or poisons in cases where signs and symptoms of digitalis toxicity are not relieved by administration of DigiFab®.
Rapid drop in serum potassium concentration may occur after treatment. Monitor frequently.
Patients with poor cardiac function may deteriorate secondary to the withdrawal of the inotropic action of digoxin by DigiFab®. Monitor frequently and provide additional inotropic support if needed. Postpone re-digitalization, if possible, until the Fab fragments have been eliminated; this may require several days or a week or longer in patients with impaired renal function.
Hypersensitivity Reactions: Anaphylaxis and hypersensitivity reactions are possible. Carefully monitor patients for signs and symptoms of an acute allergic reaction and if one occurs, stop the infusion and treat immediately with appropriate emergency medical care.
Patients with known allergies to sheep protein or those who have previously received intact ovine antibodies or Fab are particularly at risk for an anaphylactic reaction.
Do not administer DigiFab® to patients with a known history of hypersensitivity to papaya or papain unless the benefits outweigh the risks and appropriate management for anaphylactic reactions is readily available.
Use of DigiFab® in Renal Failure: The elimination half-life of DigiFab® in renal failure has not been clearly defined. Monitor patients with severe renal failure who receive DigFab® for a prolonged period for possible recurrence of toxicity. Monitoring of free (unbound) digoxin concentrations after the administration may be appropriate
Laboratory Tests: DigiFab® may interfere with digitalis immunoassay measurements. Thus, standard serum digoxin concentration measurements may be clinically misleading until the Fab fragments are eliminated from the body. This may take several days or a week or more in patients with markedly impaired renal function. If possible, obtain serum digoxin samples before DigiFab® administration to establish the level of serum digoxin at the time of diagnosis.
The total serum digoxin concentration may rise precipitously following administration of DigiFab®, but this will be almost entirely bound to the Fab fragment and not able to react with receptors in the body.
The most common adverse reactions (>7%) related to DigiFab® administration are worsening congestive heart failure (13%), hypokalemia (13%) and worsening atrial fibrillation (7%).
About BTG Pharmaceuticals
BTG Pharmaceuticals provides rescue medicines that counteract the potentially life-threatening effects associated with exposure or overexposure to certain toxins. These acute care products are typically used in emergency rooms and intensive care units to treat patients for whom there are limited or no existing treatment options. We are dedicated to delivering quality medicines that make a real difference to patients through the development, manufacture, and commercialization of pharmaceutical products. To learn more about BTG Pharmaceuticals, please visit: btgplc.com/pharmaceuticals.
For further information contact:
Chris Sampson, Corporate Communications Director
+44 (0)20 7575 1595; Mobile: +44 (0)7773 251 178
Chris Gale, Greentarget
(646) 695-2883; Mobile (203) 570-4681
i Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol January 2006, 1 (1) 19-32; DOI: https://doi.org/10.2215/CJN.00240605
iiWeiss AJ (Truven Health Analytics), Elixhauser A (AHRQ). Trends in Operating Room Procedures in U.S. Hospitals, 2001–2011. HCUP Statistical Brief #171. March 2014. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb171-Operating-RoomProcedure-Trends.pdf.
iiiBignami E, Casamassima N, Frati E, Lanzani C, Corno L, Alfieri O, Gottlieb S, Simonini M, Shah KB, Mizzi A, Messaggio E, Zangrillo A, Ferrandi M, Ferrari P, Bianchi G, Hamlyn JM, Manunta P. Preoperative endogenous ouabain predicts acute kidney injury in cardiac surgery patients. Crit Care Med. 2013 Mar; 41(3): 744–755. doi: 10.1097/CCM.0b013e3182741599
ivPullen MA, Brooks DP, and Edwards RM. Characterization of the neutralizing activity of digoxin-specific Fab toward ouabain-like steroids. J Pharmacol Exp Therap 310: 319-325, 2004.
vPullen MA, Harpel MR, Danoff TM, and Brooks DP. Comparison of non-digitalis binding properties of digoxin-specific Fabs using direct binding methods. J Immunol Methods 336: 235-241, 2008.