Table 1.
Investigational agents for the treatment of staphylococcal bacteremia in clinical trials
| Clinicaltrials.gov Identifier | Intervention | Phase | Proposed Sample Size/Enrollment | Primary Endpoints | Status | Results |
|---|---|---|---|---|---|---|
| Monotherapy | ||||||
| NCT03138733 | Ceftobiprole vs. daptomycin (with or without Aztreonam) | III | 390 | Overall success at the post-treatment evaluation (around day 70) | Active | N/A |
| NCT04775953 | Dalbavancin vs. SOC | II | 200 | Resolution of clinical signs and symptoms, clinical failure, infectious complications | Recruiting | N/A |
| NCT00062647 | Telavancin vs. SOC for uncomplicated SAB | II | 60 (approximately 50% of patients had MRSA) | Presence or absence of clinical signs and symptoms associated with SAB, metastatic complications, positive culture at TOC evaluation | Completed | 7/8 patients (88%) given telavancin were cured of infection compared to 8/9 patients (89%) given SOC. |
| NCT02208063 | Telavancin vs. SOC | III | 121 | Alive at TOC, resolution of clinical signs and symptoms, no evidence of microbiological persistence or relapse, no new metastatic infections | Completed (terminated early) | 22/47 (47%) patients given telavancin were cured of infection compared to 27/52 (52%) given SOC. |
| NCT00427076 | Trimethoprim-sulfamethoxazole (TMP/SMX) vs. vancomycin for invasive MRSA infections | III | 252 (91 had bacteremia) | Improved patient condition or cure with or without antibiotic modifications, survival at 7 days, 30-day all-cause mortality | Completed | 51/135 (38%) patients given TMP/SMX had treatment failure compared to 32/117 (27%) given vancomycin. Patients with bacteremia given TMP/SMX had increased mortality (14/41, 34%) compared to patients given vancomycin (9/50, 18%). |
| Combination therapy | ||||||
| NCT02365493 | SOC with a β-lactam antibiotic vs. SOC for patients with MRSA bacteremia | III | 358 | All-cause mortality, persistent bacteremia at day 5 or later, microbiological relapse, microbiological treatment failure | Completed | 59/170 (35%) patients in the combination group reached a primary endpoint compared to 68/175 (39%) patients given SOC. Increased risk of acute-kidney injury in the combination therapy group (P < 0.001). |
| NCT02660346 | Daptomycin with ceftaroline vs. SOC for patients with MRSA bacteremia | IV | 40 | Time to bacteremia clearance | Completed | Significantly increased risk of mortality in the SOC group compared to the combination therapy group (P = 0.028). See section 4.2.2. |
| NCT01701219 | Ceftaroline fosamil in patients with SAB or MRSA bacteremia persisting 72 hours after initial treatment | IV | 56 | Time to bacteremia clearance, time to defervescence, clinical outcome, mortality, readmission | Completed | Results not posted. |
| NCT00871104 | Fosfomycin and imipenem vs. vancomycin for patients with bacteremia or infective endocarditis due to MRSA | IV | 50 | Negative blood culture at 7 days | Completed | 4/8 (50%) patients given combination therapy were cured of infection compared to 3/7 (43%) patients given vancomycin. |
| NCT01898338 | Fosfomycin and daptomycin vs. daptomycin for patients with MRSA bacteremia | III | 167 | Clinical and microbiological response at week 6 | Completed | 40/74 (54%) patients given combination therapy had treatment success at TOC compared to 34/81 (42%) patients given daptomycin. |
| Novel antimicrobials and adjunctive therapies | ||||||
| NCT00063089 | Altastaph (polyclonal immunoglobulin preparation) vs. placebo, both in addition to SOC | I/II | 40 (17 with MRSA) | Safety | Completed | Adverse events included fevers, rigors, and dyspnea. Patients given Altastaph had a significantly shorter median time to fever resolution (2 days versus 7 days, P = 0.09) and a shorter median duration of hospital stay (9 days versus 14 days, P = 0.03). |
| NCT00198302 | Tefibazumab (Aurexis®) (humanized monoclonal antibody) vs. placebo, both in addition to SOC | II | 60 (15 with MRSA) | Safety, pharmacokinetics, progression of uncomplicated SAB to complicated SAB, microbiological relapse, mortality | Completed | 2/30 (7%) patients given tefibazumab reached a primary endpoint compared to 4/30 (13%) patients given a placebo (P = 0.455). 12/30 (40%) patients given tefibazumab had at least one SAE, compared to 9/30 (30%) given a placebo. |
| NCT02357966 | 514G3 (human monoclonal antibody) vs. placebo, both in addition to SOC | I/II | 16 (Phase I). 52 (Phase II). 6 patients in phase I had MRSA. | Safety, tolerance, maximum tolerated dose (phase I). Duration of hospitalization, incidence of severe-adverse effects (phase II) | Completed | No adverse events attributed to the experimental treatment were reported in phase I. 56% relative risk reduction for the incidence of S. aureus related SAEs for patients given 514G3 compared to placebo (P = 0.23). Duration of hospitalization was decreased in patients given 51463 compared to placebo (8.6 ± 7 days for patients given 514G3, 12.7 ± 9 days for patients given a placebo, (P = 0.092) |
| NCT03162250 | DSTA4637S (antibody-antibiotic conjugate) vs placebo, both in addition to SOC | II | 27 | Incidence of adverse events | Completed | Full results not yet available. See section 4.3.4. |
| NCT03089697 | SAL-200 (anti-staphylococcal lysin) vs. placebo, both in addition to SOC | II | 25 | Incidence of adverse events | Completed (terminated early) | 10/12 (83%) patients given SAL-200 had a TEAE compared to 12/13 (92%) patients given a placebo. |
| NCT03163446 | Exebacase (CF-301) (anti-staphylococcal lysin) vs. placebo, both in addition to SOC for patients with SAB or infective endocarditis | II | 121 (37 with MRSA) | Incidence of adverse events, clinical outcome at day 14, pharmacokinetics | Completed | 50/71 (70%) patients given exebacase were clinical responders compared to 27/45 (60%) patients given a placebo (P = 0.31). 20/27 (74%) patients with MRSA given exebacase were clinical responders compared to 5/16 (31%) patients with MRSA given a placebo (P = 0.01). |
| NCT04160468 | Exebacase (CF-301) (antistaphylococcal lysin) vs. placebo, both in addition to SOC for patients with SAB or infective endocarditis | III | 348 | Clinical response at day 14, treatment-emergent adverse events through day 60 | Recruiting | N/A |
MRSA – methicillin-resistant Staphylococcus aureus; N/A – not applicable; SAB – Staphylococcus aureus bacteremia; SAEs – severe adverse events; SOC – standard of care; TEAE – treatment-emergent adverse event; TMP/SMX – trimethoprim/sulfamethoxazole; TOC – test-of-cure