Pilot clinical trial of an anti-TNF alpha monoclonal antibody for the treatment of septic shock.
OBJECTIVE
To determine the safety and pharmacokinetics of an anti-tumour necrosis factor (TNF alpha) monoclonal antibody in the treatment of septic shock, and to evaluate the biological evolution of cytokine response.


METHODS
Open-label, prospective, pilot trial with escalating doses of a murine monoclonal antibody (B-C7) directed against TNF alpha.


METHODS
University medical centre intensive care unit.


METHODS
Nine patients with septic shock, who received standard supportive care and antimicrobial therapy in addition to the anti-TNF alpha antibody.


METHODS
Patients were treated intravenously with one of three escalating doses of B-C7 monoclonal antibody (MoAb): 0.4 mg/kg, 0.8 mg/kg, 1 mg/kg.


RESULTS
MoAb was well tolerated despite the development of human anti-mouse antibodies (HAMA) for each patient; B-C7 plasma levels were dose-dependent. At study entry, TNF alpha and IL-6 levels were detected in six and seven patients respectively; IL-1 levels were low and interferon-gamma was undetectable.


CONCLUSIONS
No side effects were noted during treatment regardless of the dose used; however, further studies are needed to determine the clinical efficacy of this agent in septic shock.
Boillot
A
A
Department of Anaesthesiology and Intensive Care, University Hospital, Besançon, France.
Capellier
G
G
Racadot
E
E
Wijdenes
J
J
Herve
P
P
Barale
F
F
D018806:APACHE; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012772:Shock, Septic / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*