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Updated: Jun 25, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Soluble human complement receptor 1 limits ischemic damage in cardiac surgery patients at high risk requiring
Harold L Lazar1, Paula M Bokesch, Frederick van Lenta
1Department of Cardiothoracic Surgery, Boston University School of Medicine and Boston Medical Center, Boston, Mass 02118, USA. harold.lazar@bmc.org
Insights
Soluble human complement receptor type 1 (TP10) effectively inhibited complement activation during cardiac surgery but did not improve overall patient outcomes. However, TP10 significantly reduced mortality and myocardial infarction in male patients.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Pharmacology
Background:
- Cardiopulmonary bypass (CPB) triggers complement activation, increasing morbidity and mortality in high-risk cardiac surgery patients.
- Soluble human complement receptor type 1 (TP10) is a potent inhibitor of complement activation.
Purpose of the Study:
- To evaluate the efficacy of TP10 in reducing morbidity and mortality in high-risk patients undergoing cardiac surgery on CPB.
- To assess the impact of TP10 on key composite endpoints including death, myocardial infarction, and prolonged support.
Main Methods:
- A randomized, multicenter, prospective, placebo-controlled, double-blind study involving 564 high-risk patients.
- Patients received an intravenous bolus of TP10 (1, 3, 5, or 10 mg/kg) or placebo before CPB.
- Primary endpoint: composite of death, myocardial infarction, prolonged intra-aortic balloon pump support, and prolonged intubation.
Main Results:
- TP10 significantly inhibited complement activity during and after CPB, with inhibition lasting up to 3 days.
- No significant difference in the primary composite endpoint was observed between the TP10 and placebo groups (31.4% vs 33.7%, P=0.31).
- In male patients, TP10 significantly reduced the composite endpoint by 30% (P=0.025), death or MI by 36% (P=0.026), and prolonged IABP support by 100% (P=0.019). No benefits were observed in female patients.
Conclusions:
- TP10 effectively inhibits complement activation during CPB but did not improve the overall primary composite endpoint.
- TP10 demonstrated a significant reduction in mortality and myocardial infarction specifically in male patients undergoing cardiac surgery.
- The study highlights a potential sex-specific benefit of TP10 in mitigating adverse events during CPB, warranting further investigation.
Background:
This study was undertaken to determine whether soluble human complement receptor type 1 (TP10), a potent inhibitor of complement activation, would reduce morbidity and mortality in high-risk patients undergoing cardiac surgery on cardiopulmonary bypass (CPB).
Methods:
This was a randomized multicenter, prospective, placebo-controlled, double-blind study in which 564 high-risk patients undergoing cardiac surgery on CPB received an intravenous bolus of TP10 (1, 3, 5, 10 mg/kg) or placebo immediately before CPB. The primary endpoint was the composite events of death, myocardial infarction (MI), prolonged (> or =24 hours) intra-aortic balloon pump support (IABP), and prolonged intubation.
Results:
TP10 significantly inhibited complement activity after 10 to 15 minutes of CPB and this inhibition persisted for 3 days postoperatively. However, there was no difference in the primary endpoint between the 2 groups (33.7% placebo versus 31.4% TP10; P=0.31). The primary composite endpoint was, however, reduced in all male TP10 patients by 30% (P=0.025). TP10 reduced the incidence of death or MI in males by 36% (P=0.026), the incidence of death or MI in CABG males by 43% (P=0.043) and the need for prolonged IABP support in male CABG and valve patients by 100% (P=0.019). There was, however, no improvement seen in female TP10 patients. There were no significant differences in adverse events between the groups.
Conclusions:
TP10 effectively inhibits complement activation during CPB; however, this was not associated with an improvement in the primary endpoint of the study. Nevertheless, TP10 did significantly decrease the incidence of mortality and MI in male patients.
