Methods

randomized controlled trial

Random sequence generation: method of randomization unspecified

Allocated concealment: not described

Blinding: not described

Year of conduct of the trial not reported

Participants

• N = 39

• Phenytoin group (grade II ulcers = 15); Duoderm group (grade II ulcers = 13); triple antibiotic ointment group (grade II ulcers = 11)

• Setting: Veterans Administration nursing home, USA

• Numbers of men and women not clearly reported

• Mean age of participants: phenytoin group = 75.5 years; Duoderm group = 78.4 years; triple antibiotic ointment group = 76.5 years

• Inclusion criteria: age > 60 years, with a grade II decubitus ulcer. (A grade II decubitus ulcer is defined by the Agency for Health Care Policy and Research (AHCPR) Pressure Ulcer Guideline panel (AHCPR 1992) as "a partial thickness skin loss presenting as an abrasion, blister, or shallow crater involving the epidermis and/or dermal skin layers.")

• Exclusion criteria:participants with signs and symptoms of wound infection at the start of treatment, anaemia, malnutrition, folate deficiency, chronic use of immunosuppressant medications (e.g. prednisone), immobility (i.e. spinal cord injuries), those receiving oral phenytoin for any concurrent medical problem, or a history of adverse effects caused by phenytoin

Interventions

• Phenytoin group: the ulcers were debrided as necessary, cleansed with 0.9% NaCl and hydrogen peroxide, dried, and covered with 100 mg phenytoin suspension daily. A single 100 mg phenytoin capsule was opened and placed in a small plastic dosage administration cup containing 5 mL of sterile 0.9% NaCl to form a phenytoin–NaCl suspension. Sterile gauze was then soaked in the suspension and placed over the wound, followed by a layer of dry sterile gauze. Treatment continued until total closure of the ulcer occurred, without evidence of residual exudate or inflammation.

• Duoderm group: the ulcers were debrided as necessary, cleansed with 0.9% NaCl and hydrogen peroxide, and dried; then the protective backing from the Duoderm dressing pad was removed and the pad placed over the wound with the edges extending 1¼ inch beyond the wound. The dressings were checked at each shift and left in place for up to 7 days, unless they became uncomfortable, leaked, or clinical signs of infection were detected. The dressings were continued for 1‐2 weeks after apparent wound healing had occurred.

• Triple antibiotic ointment group: the ulcers were debrided as necessary, cleansed with 0.9% NaCl and hydrogen peroxide, and dried. Triple antibiotic ointment was then applied to the ulcer in a uniform layer, followed by a sterile gauze covering. This dressing was checked and changed daily, except in cases that required removal and reapplication (e.g. when spillage, contamination, or patient bathing).

Outcomes

• Time to complete healing         

• Time to formation of granulation tissue

• Serum phenytoin sodium concentrations

• Adverse treatment effect

• Pain

Duration of follow‐up: 90 days

Notes

Funding source: did not report the sources of funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quotation: "The patients were matched for age, gender, and size and severity of wounds and placed in one of the three groups based on the treatment preference of the randomly assigned physician prescribing the treatment plan."

Allocation concealment (selection bias)

Unclear risk

No details provided

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No details provided

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No details provided

Incomplete outcome data (attrition bias)
All outcomes

High risk

8 participants did not complete the study. In the phenytoin group, 1 participant had ulcers that continually recurred shortly after healing, and 2 participants died. 3 participants dropped out of the Duoderm group: 1 left the facility, and 2 died. In the triple antibiotic ointment group, 2 participants did not complete the study because 1 transferred to another facility and 1 died. No participants withdrew from the study secondary to adverse treatment effects. Hence, the final analysis sample did not include them in further analyses.

Selective reporting (reporting bias)

Low risk

Study aims were stated in the paper and reported in the Results section.

Other bias

Unclear risk

Unclear

Methods

randomized controlled trial

Random sequence generation: used a random‐number table

Allocated concealment: delivered in an opaque sealed envelope bearing only the number of the participant

Blinding: blinding of personnel and outcome assessors, not participants

The study took about 10 months from proposal to final analysis (November 2001‐September 2002)

Participants

• N = 83

• Phenytoin group (grade I ulcers = 9; grade II = 19); hydrocolloid dressing group (grade I = 12; grade II = 16); simple dressing group (grade I = 10; grade II = 17)

• Information on power calculation: before the study, the authors assumed response rates of 30%, 40% and 80% for simple dressing, phenytoin cream and hydrocolloid dressing, 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.

• Setting: family homes or nursing homes, Iran

• Numbers of men and women not clearly reported

• Mean age of participants (years ± SD): phenytoin group (36.5 ± 4.99); hydrocolloid dressing group (36.81 ± 6.71); simple dressing group (36.6 ± 6.17)

• Inclusion criteria: paraplegia caused by spinal cord injury; pressure ulcer grade I and II according to Shea classification (Shea 1975) or National Pressure Ulcer Advisory Panel (NPUAP 1989); patient's informed consent; smoothness of ulcer area to establish whether adhesive could be used at the site

• Exclusion criteria: addiction; heavy smoking (more than 20 cigarettes a day or more than 10 packs per year; concomitant chronic disease (e.g. diabetes mellitus or frank vascular disease such as Buerger's disease)

Interventions

Necrotic tissue was debrided before treatment; all debridements preceded ulcer tracing and assignment of participants to the trial groups. No debridement was allowed after treatment had started. No concomitant topical or systemic antibiotic, glucocorticoid or immunosuppressive agents were allowed during the treatment period.

• Phenytoin group: daily dressing and cleaning of ulcer were similar to the simple dressing group (see later), except that a thin layer of phenytoin cream was applied to the ulcer before the dressing was applied.

• Hydrocolloid group: daily dressing and cleaning of ulcer were similar to the simple dressing group, after which the hydrocolloid adhesive dressing was applied to the ulcer area. The adhesive dressings were changed twice a week.

• Simple dressing group: the ulcer was cleaned and washed 3 times with normal saline, then dried with a sterile gauze and, depending on the size of the ulcer, covered with wet saline gauze dressing. This was done twice a day.

Outcomes

• Complete healing

• Partial healing

• Without improvement

• Worsening

• Adverse treatment effect

Duration of follow‐up: 6 months

Notes

Funding source: received financial support from the Jaonbazan Medical and Engineering Research Center

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quotation: "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)."

Allocation concealment (selection bias)

Low risk

Quotation: "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 [simple dressing], PC [phenytoin cream] or HD [hydrocolloid dressing] method would be used, then the appropriate intervention commenced."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quotations: "Because significant differences among the three treatment methods precluded blinding, the patients were also aware of the treatment methods."

"the author who enrolled the patients to the study was blind to treatment assignment."

"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."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quotation: "The author who finally assessed the outcomes was also blind to the trial group of each patient."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quotation: "All patients completed the study and there were no losses to follow‐up, no treatment withdrawals, no trial group changes and no major adverse events"

Selective reporting (reporting bias)

Low risk

Study aims were stated in the paper and reported in Results section.

Other bias

Unclear risk

Funding: the study was supported by the Jaonbazan Medical and Engineering Research Center, the medical and research section of the official governmental body responsible for spinal cord injury war victims.

Methods

A prospective, randomized, double‐blind clinical trial

Random sequence generation: computer‐generated randomization list

Allocated concealment: prepared and labelled using the randomization number by pharmacists of the institution's pharmacy

Blinding: personnel, outcome assessors, and  participants blinded

The study was carried out between October 2005‐November 2006.

Participants

• N = 26

• Phenytoin group (grade II ulcers = 12); simple dressing group (grade II = 14)

• Setting: Christian Medical College (CMC), Vellore, a tertiary care teaching hospital in south India

• Numbers of men and women not clearly reported

• Mean age of participants (years ± SD): phenytoin group (34.25 ±18.12); simple dressing group (31.64 ± 12.27)

• Inclusion criteria: paraplegic participants aged between 10‐55 years, presenting with grade II pressure ulcers without necrotic tissue

• Exclusion criteria: people with anaemia, hypoalbuminaemia, elevated serum creatinine, abnormal liver function tests, history of smoking, peripheral vascular disease, diabetes mellitus, malignancy, connective tissue disorders and psychiatric illness

Interventions

• Phenytoin group: phenytoin solution (50 mg/mL, Park‐Davis) was diluted using normal saline (0.9% NaCl, CMC pharmacy) to prepare a phenytoin solution (5 mg/mL). At this concentration the pH was 7.3–7.4. The preparation was indistinguishable from normal saline in presentation, colour, density, and odour. Participants received sterile gauge soaked with phenytoin solution for dressing their ulcers once daily for 15 days.

• Simple dressing group: participants received sterile gauge soaked with normal saline for dressing their ulcers once daily for 15 days.

Outcomes

• Reduction in Pressure ulcer scale for healing (Thomas 1997)

• Reduction in ulcer size

• Reduction in ulcer volume

• Systemic absorption of topical phenytoin

• Adverse treatment effect

Duration of follow‐up: 16 days

Notes

Funding source: received financial support from intramural research funds of Christian Medical College, Vellore, India

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quotation: "Patients were randomly assigned to the treatment and control groups using a computer‐generated randomization list."

Allocation concealment (selection bias)

Low risk

Quotation: "Treatment (phenytoin solution) and control solutions (normal saline) were prepared and labelled using the randomization number by pharmacists of our institutional pharmacy."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quotations: "The preparation was indistinguishable from the normal saline in presentation, color, density, and odor."

"The nursing staff who administered pressure ulcer dressings were blind to treatment assignment."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quotation: "All evaluations were carried out by a single investigator who was blind to the type of intervention."

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Quotation: " . . . two patients in the treatment group were lost to follow‐up because of discharge from the hospital at patient's request. Hence, the final analysis sample comprised 12 patients in the treatment group and 14 patients in the control group"

Selective reporting (reporting bias)

Low risk

Study aims were stated in the paper and reported in the Results section.

Other bias

Unclear risk

Funding source: received financial support from intramural research funds of Christian Medical College, Vellore, India.