Collagenase Ointment Application at 24- Versus 48-Hour Intervals in the Treatment of Pressure Ulcers: A Randomized Multicenter Study

Discussion

The efficacy of collagenase ointment has been proven in the treatment of ulcers in placebo-controlled studies^[5,15,16] as well as in comparative studies of collagenase versus fibrinolysin/ DNase,^[18] hydrocolloid^[19] or other topical treatments.^[17]

The efficacy of collagenase ointment involves not only ulcer area reduction, but reduction in pain intensity and exudate production, and increase in granulation tissue formation. In the present series, ulcers healed completely in 24.4% of patients, the ulcer area decreased remarkably in 72.9% of patients, and in only 5.2% of patients did the ulcer area not show the expected reduction. Ulcer healing is largely dependent upon nutritional status, assessed by measuring serum albumin levels. Serum albumin levels 3.5 g/dl are indicative of malnutrition.^[7] In the present study, most patients (78.7%) had malnutrition, a widely recognized poor prognostic factor related to ulcer occurrence in bedridden patients.^{[23,24,25,26]}

The recommended use of collagenase ointment consists of daily application of a 1 to 2mm thick layer on the ulcer bed (according to the manufacturers). Daily care of chronic ulcers in hospitalised or institutionalised patients represents an extra effort for hospital staff, and current trends consisting of home hospitalisation may effectively represent an additional workload for health workers. Home hospitalisation units have recognized many advantages (such as less risk of nosocomial infection, improved comfort and privacy for the patient, active patient participation in decision-making related to his/her condition, and decreased episodes of confusional state among elderly patients), and comprise physicians, nursing staff, emergency services on call, and social workers. The equivalent efficacy of collagenase ointment administered at 48-hour intervals instead of daily application could imply an optimisation of health resources.

In the present study, we have demonstrated that once granulation tissue has covered at least 11 to 30% of the ulcer surface, application of collagenase ointment at 48-hour intervals had an equivalent clinical efficacy compared with daily application. Although the loss of statistical power because of dropouts throughout the study did not allow the establishment of a statistically significant equivalence beyond 1 month following the presence of granulation tissue on 11 to 30% of the ulcer bed, a clinical equivalence should exist on the basis of ulcer area reduction observed with both therapeutic regimens throughout the study period (fig. 2). This therapeutic efficacy could probably be extended throughout the healing process.

Equivalence intervals should be established in advance. In the absence of guidelines in the literature, an equivalence interval of ± 20% mean reduction in ulcer area was considered adequate from a clinical standpoint. Since the mean area of ulcers evaluated in the present study was 14.6cm² (that is, equal to 2.15cm considering the ulcer shape as a hypothetical circumference), a difference of ± 20% would cause a change of ± 2.2mm in the radius of this circumference, which has a minimum clinical relevance.

Collagenase fosters granulation tissue formation and reorganization of definitive collagen.^[4,5,10] It has been recognized that excessive wound handling can delay granulation tissue formation or damage existing granulation tissue. This fact could explain why application of collagenase ointment at 48-hour intervals conferred the same therapeutic benefit as daily application in the present study.

Both treatment groups were comparable given that the inclusion criterion was restricted to patients aged 55 years or over, but at the cost of a high index of dropouts (34.3%). Of these, 37.1% were due to deaths. The analysis of the risk of study discontinuation showed a trend to leave the study among patients treated at 48-hour intervals, although such a trend did not reach statistical significance. However, a closer look at discontinuation reasons revealed that most patients (88.2% in the 24-hour interval group and 88.8% in 48-hour interval group) abandoned the study because of death, protocol violations or discharge from the hospital, and there were no cases of discontinuation related to the dosage schedule.

Clin Drug Invest. 2000;19(6) © 2000 Adis Data Information BV

Cite this: Collagenase Ointment Application at 24- Versus 48-Hour Intervals in the Treatment of Pressure Ulcers: A Randomized Multicenter Study - Medscape - Jun 01, 2000.