First patient dosed with dalbavancin in S. aureus bacteremia trial
The trial will assess the efficacy of a two week regimen of the FDA-approved antibiotic dalbavancin in treating 100 patients with Staphylococcus aureus bacteremia.
A new Phase IIb trial (NCT04775953) to evaluate the safety and efficacy of the antibiotic dalbavancin in treating Staphylococcus aureus bacteremia has begun. The trial will enrol 200 adults hospitalised with complicated S. aureus infection at approximately 20 sites across the US.
S. aureus is a leading cause of antibiotic-resistant infection (eg, methicillin resistant S. aureus [MRSA]) and, according to the US Centers for Disease Control and Prevention (CDC), S. aureus infections caused almost 20,000 deaths in the US in 2017. The bacteria is also of particular concern in healthcare-associated infections.
S. aureus bacteremia is a blood infection caused by the S. aureus bacteria. It is associated with high morbidity and mortality and often results in serious metastatic infections such as infective endocarditis, that can further negatively impact on patient outcomes. The treatment of S. aureus bacteremia often requires patients to have daily doses of antibiotics administered intravenously for four to six weeks and thus long-term care in healthcare facilities.
“As antibiotic-resistant infections become more widespread, better and easier treatment regimens are needed to ease the burden on both healthcare providers and patients,” said Dr Anthony Fauci, Director of the US National Institute of Allergy and Infectious Diseases (NIAID), which is sponsoring the trial. “By investigating existing antibiotics for their action on a broader array of bacterial infections, we may be able to generate new treatment regimens more efficiently.”
The Phase IIb ‘Dalbavancin as an Option for Treatment of S. aureus Bacteremia (DOTS)’ trial is being led by Dr Thomas Holland of Duke University. It will enrol 200 adults who have stabilised after initial treatment of their bacteremia and randomise them 1:1 to receive the standard of care for complicated infections, including appropriate antibiotics, or two IV doses of dalbavancin. Most participants receiving dalbavancin will be given 1500mg per dose, except those with signs of kidney dysfunction, who will receive 1125mg per dose. All participants will be followed for approximately 70 days after enrolment and up to six months if they have vertebral osteomyelitis, an infection of the vertebrae.
At the end of the trial assess multiple patient outcomes will be assessed, including survival; additional complications (such as relapse) or clinical failures; drug-related adverse events; and overall quality of life. The therapeutic regimen will have met the primary endpoint of the trial if participants who received dalbavancin fare better on these metrics than those who received the current standard of care.
The antibiotic dalbavancin has strong activity against gram-positive bacteria, including MRSA, which suggests it could be an effective treatment for S. aureus bacteremia. It is currently approved by the US Food and Drug Administration (FDA) for treating acute bacterial skin and skin structure infections, including those caused by S. aureus. If the two-dose regimen being tested in this trial proves effective, it could lead to a shorter, less invasive treatment for S. aureus bacteremia that does not require an indwelling IV access for daily therapy.