The study was a randomized single blind clinical trial involving 2015 Iranian spinal cord injury (SCI) victims of the Iran-Iraq war (1980–1988). The SCI victims were accessed through the mediation and assistance of the Jaonbazan Medical and Engineering Research Center (JMERC) http://www.jmerc.ac.ir
, the medical and research section of the official governmental body responsible for SCI war victims. The study proposal was reviewed, approved and granted by JMERC.
The medical records of all 2015 subjects were studied to identify cases with pressure ulcers. Where the data were unknown or unreliable, the patients were visited at home or in victims' long term care centers. Finally, 165 pressure ulcers in 151 patients were identified. All relevant data including patient age and weight, the longevity of the ulcer before our intervention, and the size, stage and location of the ulcer, were collected by the general practitioners in the team. Next, all the patients were examined by one of the authors to confirm their eligibility for the study. The eligibility criteria were: A) Inclusion Criteria: 1. Paraplegia caused by spinal cord injury; 2. Pressure ulcer stage I and II according to Shea classification [20
] or National Pressure Ulcer Advisory Panel [21
] (Fig. ); 3. Patient's informed consent; 4. Smoothness of ulcer area to establish whether adhesive could be used at the site. Exclusion criteria: 1. Addiction; 2. Heavy smoking (more than 20 cigarettes a day or more than 10 packs per year; 3. Concomitant chronic disease (e.g. diabetes mellitus or frank vascular disease such as Buerger's disease).
Two pressure ulcer classifications.
Seventy-four ulcers in 68 patients were excluded because they did not meet these eligibility criteria: 31 ulcers (28 patients) were stage III or higher; 27 ulcers (25 patients) were excluded because of patient's smoking/addiction; 5 ulcers (5 patients) had uneven surfaces; 4 ulcers (4 patients) were excluded because of systemic diseases; and 6 patients with 7 ulcers refused to participate (Fig. ). Thus, the study sample comprised 83 patients with 91 pressure ulcers in the ischial, sacral or gluteal areas. These 91 ulcers were allocated to three different groups (30 ulcers each) by stratified randomization. Three therapeutic methods were applied as follow: simple dressing (SD), hydrocolloid dressing (HD), and adhesive and phenytoin cream (PC). Two general practitioners and nine nurses trained in treatment interventions administered the protocols.
Flow diagram of participants through each stage of the study.
The SD patients were visited twice a day, the PC patients once a day and the HD patients twice a week. All participants were visited and examined in their family homes or nursing homes by general practitioners every two weeks to ensure that the treatments were being properly applied and were consistent among the three groups. There were no differences in the facilities available for patients in family homes versus nursing homes, and all the patients had free access to victims' long term care centers.
In the SD group, the following steps were taken twice a day. The ulcer was cleaned and washed 3 times with normal saline, then dried with a sterile gauze and, depending on the size of ulcer, covered with wet saline gauze dressing. In the PC group, daily dressing and cleaning of ulcer were similar to the SD group, except that a thin layer of phenytoin cream was applied to the ulcer before the dressing was performed. In the HD group, after the ulcer had been cleaned in a similar manner to the SD group, the hydrocolloid adhesive dressing was applied to the ulcer area. The adhesive dressings were changed twice a week. Any necrotic tissue was debrided before treatment; all debridements preceded ulcer tracing and assignment of the participants to the trial groups. No debridement was allowed after treatment had started. No concomitant topical or systemic antibiotic, glucocorticoid or immunosuppressive agent was allowed during the treatment period. Fortunately, none of our patients needed debridement or the aforementioned concomitant therapies during the study period. There were no differences among the trial groups with respect to other concomitant care measures.
Every two weeks a questionnaire regarding the ulcer's status was completed by the general practitioners; and at the end of 8 weeks, the ulcers' conditions were examined blind by one author and assessed as "Complete Healing", "Partial Healing", "Without Improvement" or "Worsening". To measure each ulcer's surface area, the ulcer borders were traced on to a paper overlay. This primary schematic representation was then scanned, redrawn and measured by AutoCAD 2000 software.
The primary outcome was whether or not the ulcer was completely healed within 8 weeks. "Complete ulcer healing" was defined as: A) For stage I ulcer, intact epidermis, no red area; B) For stage II ulcers, intact dermis and epidermis, no abrasion or ulceration. Other definitions were as follows. "Partial healing" = any decrease in ulcer size compared to the baseline ulcer tracing, excluding complete healing. "Without improvement" = no change in ulcer size compared to the baseline ulcer tracing. "Worsening" = any increase in ulcer size compared to the baseline ulcer tracing. The difference in responses between patients receiving HD and patients receiving the other therapies (PC or SD) were determined [22
Before the study, we assumed response rates of 30%, 40% and 80% for SD, PC and HD, respectively. Thus, based on the 40% difference, power of 0.85, 95% confidence level and estimated follow-up loss of 10%, 29 patients were required for each study group. The number of ulcers that met the eligibility criteria totaled 91 and all were enrolled in the study.
A random-number table was used to generate the random allocation sequence, and stratified randomization was used to achieve balance between the treatment groups and subgroups (ulcer stages and locations). If a patient had more than one ulcer, all the ulcers were treated by the same method to eliminate the possible complicating factor of treatment interactions. The statistician in the team generated the random allocation sequence. He was informed of the patient list (numbers only) and the ulcer stage and location of each patient.
The treatment category for each patient was determined by the statistician and was delivered in an opaque sealed envelope bearing only the number of the patient. These sealed envelopes were delivered to the general practitioners, along with the list of patients' numbers and names. After each patient was visited, the appropriately numbered envelope was opened by the general practitioner to determine whether the SD, PC or HD method would be used, then the appropriate intervention commenced.
The authors were blind to the patients' assignment to trial groups. The general practitioners were also blind to the treatment of each patient up to the start of the study, when they opened the sealed envelopes. After intervention began, both the general practitioners and the nurses knew the trial groups, because significant differences among the three treatment methods precluded blinding. The patients were also aware of the treatment methods, although they initially had equal chances of entering any of the trial groups. Thus, the study was single-blinded and the author who enrolled the patients to the study was blind to treatment assignment. The author who finally assessed the outcomes was also blind to the trial group of each patient.
To maintain the blinded status on assessment of outcomes, the assessor examined the patients, after the ulcer dressings had been removed by the general practitioners, with no knowledge of the trial groups to which they had been assigned. The gross appearance of the ulcers without dressing, whether healed or not, did not indicate the trial group. The assessor was asked during the 8-week outcome assessment to try to identify which treatment has been administered to each patient. Overall, 27.7% of his guesses were correct (25% in the HD group, 32.1% in the PC group and 25.9% in the SD group), so they were were no better than chance; i.e. there were no significant differences among the three trial groups with respect to proportions guessed correctly (P > 0.2 in all cases).
The study proposal was designed in November 2001, and the recruitment of patients began in March 2002 and lasted about 2 months. Then the patients were allocated to the treatment groups and followed-up for another 2 months. Finally, all the collected data were analyzed within 2 months. Thus the study from proposal to final analysis took about 10 months (November 2001-September 2002). At the end of the study, all the data collected from the patients' preliminary and complementary questionnaires were analyzed by SPSS software using ANOVA and Chi square tests, and P-values of <0.05 were assumed significant. The 95% confidence intervals were also calculated and reported [23
]. For rare events (more than 20 percent of cross tabulation cells had values less than 5), Fisher's exact test was used. Based on stage and location of ulcers, subgroup analyses were performed using the same statistical tests.