By David N. Leff

In what is perhaps the largest clinical trial of its kind ever, burn-injury specialists at 32 hospitals across China report success in testing a growth-factor hormone on 300 patients with superficial and deep second-degree burns.

Their paper, in the current issue of The Lancet, dated Nov. 21, 1998, bears the title “Randomized placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor [rbFGF] for second-degree burns.“ The article's first author, and leader of the study, is Xiaobing Fu, of the Wound Healing Unit, Postgraduate Medical College, in Beijing.

The consortium enrolled 600 male and female adult patients in its study, during the first half of 1996.

The 333 subjects with partial-thickness burns through a portion of their dermis and epidermis were classified as superficial; the remaining 261 had suffered deep second-degree trauma, covering up to 10 percent of their total body surface area. Third-degree burn cases were not included in the study.

Half of the total enrolled received daily topical applications of the growth factor, starting within five days of injury. The other 300 served as placebo controls. All 300 of the treatment group completed the study, whereas six controls dropped out, two for pregnancy; four because of new injuries.

“All patients treated with rbFGF,“ the co-authors report, “had faster granulation tissue formation and epidermal regeneration than those in the placebo group.“ The superficial-wound cohort healed in 9.9 days on average; those with deep second-degree injuries took 17 days. The control patients required 12.4 and 21.2 days, respectively.

These accelerated healing times, the paper pointed out, would make for shorter hospital stays “and the patient's skin quickly becoming available for harvesting and grafting.“

Of the 168 rbFGF-treated patients with superficial second-degree burns, 161 (95.8 percent) had outcomes rated “effective.“ The 132 with deep second-degree lesions scored 94.7 percent (125 cases) effective.

The 14 “non-effective“ patients suffered side-effects including high fever, liver and kidney dysfunction, local pain and infection.

To assess healing progress, the team photographed all wounds daily, and performed punch biopsies on days three and seven. “We defined healed wounds,“ they reported, “as burns that were totally closed.“ Biopsy samples showed that “in the rbFGF group, the epidermis and dermis were almost completely regenerated ... and fibroblasts differentiated. By contrast, wounds in the placebo group typically lacked a continuous epidermis and dermis and the regenerated cells were scant, less organized, and poorly differentiated.“

Now, the paper summed up, “more than 1.5 years after treatment stopped, there were no complications and no clinical evidence of neoplasias in the healed wounds. None of our patients had hypertropic [non-malignant tissue bulk] scarring . . . after use of rbFGF.“

Basic fibroblast growth factor, the Lancet paper noted, is a 146-amino acid polypeptide that “stimulates proliferation and differentiation of endothelial cells and fibroblasts, and has a key part in regeneration of granulation tissues.“

The rbFGF used in the burn-injury study was produced by the Torita Bio-Pharma Industry Co., of Zhuhai, China.

Fu and his co-authors concluded cautiously that the biological effects of the treatment “do, however, require further elucidation.“

U.S. Burn Experts Assess Chinese Experience

“To my knowledge, that is a very big trial for burns,“ observed clinical research specialist Gary Gentzkow. “The problem for a multicenter study in burns is actually getting meaningful data, because people tend to do everything differently. You can partially overcome that objection with large numbers, which the Lancet authors seem to have done. But I'd want to look at that study in great detail to decide whether you can believe it.“

Gentzkow, a pioneer fibroblast growth factor researcher, is executive director of worldwide medical affairs at Advanced Tissue Sciences Inc., in La Jolla, Calif.

Commenting on the Chinese paper, he observed, “FGF does not, on a theoretical basis, seem to be the ideal molecule to think of for partial-thickness burns, where your principal objective is to epithelialize the wound. Also, you'd think, if you were going to the trouble of doing a recombinant protein, you'd make it human instead of bovine.“

And burn specialist Scott Somers also told BioWorld Today, “I am unaware of a clinical trial of this size, so it is interesting that [the Chinese] were able to do this at multiple clinical centers.“

Somers is program administrator for the Trauma and Burn Injury Program at the National Institute of General Medical Sciences (NIGMS), on the National Institutes of Health campus, in Bethesda, Md.

“I'm also unaware,“ he added, “[of] any U.S. pharmaceutical house currently pushing [rbFGF] therapy.“

He continued: “There are widespread clinical studies in any number of growth-factors in cocktails - not just one factor - with no success thus far. So, I think this Lancet trial is somewhat surprising. I'm sure it will be scrutinized very carefully, because a lot of people have tried this rbFGF treatment.“

Scar-Free Healing Attractive

Somers was particularly intrigued by the Chinese finding that scientists had encountered no scarring, which he characterized as a “downside“ in growth-factor treatment. “They are controlling the wound process very carefully, obviously,“ he said. “You don't want excessive fibroblast proliferation and migration that will lead to hypertropic scarring, which is a huge problem in a serious burn.“

When it comes to skin grafting for third-degree, full-thickness burns, Somers said, “you have to put something back in place of the destroyed tissue. That's where the split-thickness skin graft - autografts, or cadaver skin or artificial skin, which is prevalent in the U.S. - comes in.

“Still,“ he said, “once you put that scaffolding there, whatever it is, there's a number of studies here that are looking at growth factors like this to increase the rate of healing.“ n