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A randomized, placebo-controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings.
J Thorac Cardiovasc Surg. 2005 Feb; 129(2):423-8.JT

Abstract

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.

Authors+Show Affiliations

University of Toronto, Toronto, Ontario, Canada. shaf.keshavjee@uhn.on.ca <shaf.keshavjee@uhn.on.ca>No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

15678055

Citation

Keshavjee, S, et al. "A Randomized, Placebo-controlled Trial of Complement Inhibition in Ischemia-reperfusion Injury After Lung Transplantation in Human Beings." The Journal of Thoracic and Cardiovascular Surgery, vol. 129, no. 2, 2005, pp. 423-8.
Keshavjee S, Davis RD, Zamora MR, et al. A randomized, placebo-controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings. J Thorac Cardiovasc Surg. 2005;129(2):423-8.
Keshavjee, S., Davis, R. D., Zamora, M. R., de Perrot, M., & Patterson, G. A. (2005). A randomized, placebo-controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings. The Journal of Thoracic and Cardiovascular Surgery, 129(2), 423-8.
Keshavjee S, et al. A Randomized, Placebo-controlled Trial of Complement Inhibition in Ischemia-reperfusion Injury After Lung Transplantation in Human Beings. J Thorac Cardiovasc Surg. 2005;129(2):423-8. PubMed PMID: 15678055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomized, placebo-controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings. AU - Keshavjee,S, AU - Davis,R D, AU - Zamora,M R, AU - de Perrot,M, AU - Patterson,G A, PY - 2005/1/29/pubmed PY - 2005/4/15/medline PY - 2005/1/29/entrez SP - 423 EP - 8 JF - The Journal of thoracic and cardiovascular surgery JO - J Thorac Cardiovasc Surg VL - 129 IS - 2 N2 - 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. SN - 0022-5223 UR - https://www.unboundmedicine.com/medline/citation/15678055/A_randomized_placebo_controlled_trial_of_complement_inhibition_in_ischemia_reperfusion_injury_after_lung_transplantation_in_human_beings_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022522304011444 DB - PRIME DP - Unbound Medicine ER -