A randomized, placebo-controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings.
OBJECTIVE
Complement activation has been shown to play a significant role in ischemia-reperfusion injury after lung transplantation. TP-10 (soluble complement receptor 1 inhibitor) inhibits the activation of complement by inactivating C3a and C5a convertases. This was a clinical trial of TP-10 to reduce ischemia-reperfusion injury in lung transplantation.


METHODS
In a randomized, double-blinded, multicenter, placebo-controlled trial, 59 patients from four lung transplant programs received TP-10 (10 mg/kg, n = 28) or placebo (n = 31) before reperfusion. This dose achieved 90% complement inhibition for 24 hours, and activity had returned toward normal by 72 hours.


RESULTS
At 24 hours, 14 of 28 patients in the TP-10 group (50%) were extubated, whereas only 6 of 31 patients in the placebo group (19%) were (P = .01). The total times on the ventilator and in the intensive care unit both tended to be shorter in the TP-10 group, but these differences did not achieve statistical significance. Among patients requiring cardiopulmonary bypass (n = 5 in placebo group and n = 7 in TP-10 group), the mean duration of mechanical ventilation was reduced by 11 days in the TP-10 group (10.6 +/- 5.0 days vs 21.5 +/- 5.9 days in placebo group, P = .2). Operative deaths, incidences of infection and rejection, and length of hospital stay were not significantly different between the two groups.


CONCLUSIONS
Short-term complement inhibition with TP-10 led to early extubation in a significantly higher proportion of lung transplant recipients. The effect of TP-10 was greater among patients undergoing cardiopulmonary bypass, with a large reduction in ventilator days. Complement inhibition thus significantly decreases the duration of mechanical ventilation and could be useful in improving the outcome of lung transplant recipients.
Keshavjee
S
S
University of Toronto, Toronto, Ontario, Canada. shaf.keshavjee@uhn.on.ca <shaf.keshavjee@uhn.on.ca>
Davis
R D
RD
Zamora
M R
MR
de Perrot
M
M
Patterson
G A
GA
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass; D003169:Complement Inactivator Proteins / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D003165:Complement System Proteins / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007902:Length of Stay; D008171:Lung Diseases / Q000401:mortality / Q000601:surgery; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D009656:North America; D010101:Oxygen Consumption / Q000187:drug effects; D011183:Postoperative Complications / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control*; D011951:Receptors, Complement / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control*; D012121:Respiration, Artificial; D013530:Surgical Wound Infection / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D016019:Survival Analysis; D016896:Treatment Outcome
D015415:Biomarkers; D003169:Complement Inactivator Proteins; D011951:Receptors, Complement; C082885:soluble complement inhibitor 1; D003165:Complement System Proteins