Pilot multicenter, genotype-based, randomized, double-blind, placebo-controlled trial of propranolol to reduce initial pain symptoms in patients with major burn injury

More than 70,000 people are admitted to US hospitals each year after major burn injury. Achieving adequate pain control in these patients remains a substantial clinical challenge. Even with the use of “best practice” medications, additional methods of decreasing burn pain are urgently needed. We performed a pilot multicenter, genotype-guided, randomized, double-blind, placebo-controlled trial of propranolol to reduce pain in the initial weeks after major thermal burn injury. Eligible and consenting patients admitted to network burn centers within 72 hours of acute thermal burn injury were genotyped at rs4818. After two days of initial interview assessments, genotype eligible patients were randomized to 120 mg twice daily of propranolol vs. placebo. Study drug was continued until three weeks after hospital discharge. The primary outcome measure was daily pain score (0 – 10 numeric rating pain score) recorded by the patient during the first 19 days after study drug initiation. Study feasibility was evaluated via consent and protocol completion rates, while study acceptability was assessed via qualitative analyses. Efficacy evaluations were performed to generate estimates of potential therapeutic benefit using mixed effects models with random intercepts to account for subject effects and the correlation among repeated measurements within a subject. To date, 73% (44/60) of eligible patients consented to complete initial interview evaluation and genotyping for the study. Seventy nine percent (34/43) were eligible based on genotype and were subsequently enrolled in the RCT. Eighty two percent (28/34) both tolerated study drug and underwent primary outcome assessments. The great majority (91%) of study participants agreed with the statement, “Had I know in advance what participating would be like for me, I still would have agreed.” Pilot enrollment (n=40 completing trial) will conclude by early 2011; estimates of potential therapeutic benefit based on efficacy analyses will be presented. More than 70,000 people are admitted to US hospitals each year after major burn injury. Achieving adequate pain control in these patients remains a substantial clinical challenge. Even with the use of “best practice” medications, additional methods of decreasing burn pain are urgently needed. We performed a pilot multicenter, genotype-guided, randomized, double-blind, placebo-controlled trial of propranolol to reduce pain in the initial weeks after major thermal burn injury. Eligible and consenting patients admitted to network burn centers within 72 hours of acute thermal burn injury were genotyped at rs4818. After two days of initial interview assessments, genotype eligible patients were randomized to 120 mg twice daily of propranolol vs. placebo. Study drug was continued until three weeks after hospital discharge. The primary outcome measure was daily pain score (0 – 10 numeric rating pain score) recorded by the patient during the first 19 days after study drug initiation. Study feasibility was evaluated via consent and protocol completion rates, while study acceptability was assessed via qualitative analyses. Efficacy evaluations were performed to generate estimates of potential therapeutic benefit using mixed effects models with random intercepts to account for subject effects and the correlation among repeated measurements within a subject. To date, 73% (44/60) of eligible patients consented to complete initial interview evaluation and genotyping for the study. Seventy nine percent (34/43) were eligible based on genotype and were subsequently enrolled in the RCT. Eighty two percent (28/34) both tolerated study drug and underwent primary outcome assessments. The great majority (91%) of study participants agreed with the statement, “Had I know in advance what participating would be like for me, I still would have agreed.” Pilot enrollment (n=40 completing trial) will conclude by early 2011; estimates of potential therapeutic benefit based on efficacy analyses will be presented.