Phase Ⅳ clinical trial for external use of recombinant human granulocyte-macrophage colony-stimulating factor gel in treating deep partial-thickness burn wounds

Objective To evaluate the clinical efficacy and safety of external use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) gel on deep partial-thickness burn wounds. Methods Sixty-eight hospitals in our country including our unit performed a phase Ⅳ clinical trial for rhGM-CSF gel in patients (conforming to the study criteria) with deep partial-thickness burn wounds from November 2010 to July 2012. Multicenter, randomized, positive-homogenous-controlled, and open trial method was used in the trial, and patients from 10 hospitals were grouped into the positive-homogenous-controlled trial, while patients from the other 58 hospitals were grouped into open trial. (1) Controlled trial. Patients were divided into rhGM-CSF group and conventional treatment group (CT) with the ratio of 1∶1 according to the stratified randomization method. Wounds of patients in rhGM-CSF group were coated with rhGM-CSF gel, and wounds of patients in group CT were covered by gauze with iodophor. Scores of wound exudate and wound edge response before treatment and on treatment day (TD) 2, 4, 8, 10, 14, 20, and 28 were conventionally evaluated. Wound healing rates on TD 8, 10, 14, 20, and 28 were calculated. Complete wound healing time and overall efficiency including cure, excellence, progress, and invalid situation on TD 28 were recorded. Safety indexes including vital signs and laboratory test indexes before and during treatment, and adverse reactions during treatment were observed. (2) Open trial. Wounds of patients in this trail were all coated with rhGM-CSF gel. Complete wound healing time, overall efficiency, and safety indexes of patients were recorded as in controlled trial. Data were processed with CMH-χ² test, Fisher′s exact test, signed rank sum test, paired t test, Log-Rank test, and Wilcoxon rank sum test. Results (1) Controlled trail. A total of 366 patients from 10 hospitals were included in this trial, and 358 cases with 177 cases in rhGM-CSF group and 181 cases in group CT finished the trial. There were no statistically significant differences in gender, age, injury characteristics, and combined medication situation between patients in two groups (χ²=1.510, with t values from 0.458 to 0.820, P values above 0.05). Scores of wound exudate of patients in two groups were similar before treatment and on TD 2, 20, and 28 (t=0.420, with Z values from 0.735 to 1.939, P values above 0.05). Scores of wound exudate of patients in rhGM-CSF group were significantly lower than those in group CT on TD 4, 8, 10, and 14 (with Z values from 2.054 to 2.580, P values below 0.05). Scores of wound edge response of patients in two groups were similar before treatment and on each TD (t=0.340, with Z values from -1.147 to 1.874, P values above 0.05). Wound healing rate of patients in rhGM-CSF group was significantly higher than that in group CT on each TD (with Z values from 2.630 to 5.235, P values below 0.01). The complete wound healing time of patients in rhGM-CSF group was (16.93±0.40) d, which was significantly shorter than that in group CT[(19.88±0.41) d, χ²=26.732, P<0.001]. At last, 171 (96.61%) patients were completely cured in rhGM-CSF group, while excellence, progress, and invalid results were achieved in 3 (1.69%), 1 (0.56%), and 2 (1.13%) patients, respectively. Whereas, 161 (88.95%) patients were completely cured in group CT, while excellence, progress, and invalid results were achieved in 11 (6.08%), 5 (2.76%), and 4 (2.12%) patients, respectively. Total efficacy of patients in rhGM-CSF group was significantly higher than that in group CT (χ²=5.784, P<0.05). Levels of vital signs and laboratory test indexes of patients in two groups before and during treatment were similar. There were no statistically significant differences in adverse reaction or drug-related adverse reaction between patients in two groups during treatment (with P values above 0.05). (2) Open trial. A total of 2 380 patients were enrolled in, and 2 329 patients finished the trial. The complete wound healing time of patients was (16.28±0.10)d. At last, 2 257 (96.91%) patients were totally cured, while excellence, progress, and invalid results were achieved in 36 (1.55%), 16 (0.69%), and 20 (0.86%) patients, respectively. Vital signs and laboratory test indexes of patients before and during treatment were similar. The drug-related adverse reaction was observed in 44 patients (1.89%). Conclusions External use of rhGM-CSF gel on deep partial-thickness burn wounds can promote wound healing and is safe for clinical use.