Benhamou 2002.

Methods	Study design: Single centre RCT Sample size calculation: Yes ITT analysis: Yes Ethics and informed consent: Kremlin‐Bicetre, France Registration number and name of registry: Not stated
Participants	Population: Children with a malignancy, who were candidates for high dose chemotherapy and autologous or allogeneic bone marrow transplantation Setting: Paediatric Bone Marrow Transplantation unit at the Gustave Roussy Institute, Villejuif, France Number: A total of 113 patients were randomised, 57 in the 15‐day group and 56 in the 4‐day group. There was 1 post‐randomisation exclusion, results were reported for 112 participants (56 in each group) Age: 15‐day group: median 5 years, range 1‐22 years. 4‐day group: median 7 years, range 2‐19 years Gender (male:female): 15‐day group: 33:23. 4‐day group: 25:31 Skin complexion: 15‐day group: white 43/56; 'mat' 10/56; black 3/56. 4‐day group: white 47/56, 'mat' 6/56, black 3/56 Known allergies to dressings: Not stated Known history of current BSI: Not stated Inclusion criteria: Children with a malignancy, who were candidates for high dose chemotherapy and autologous or allogeneic bone marrow transplant. A qualitative culture of the skin at the catheter entry site was performed before randomisation: only children with a negative culture for Staphyloccus epidermis were eligible Exclusion criteria: Children were only included once in the trial. Those treated with the busulfan‐thiotepa conditioning regimen and those who already had grade ≥ 2 cutaneous toxicity at the catheter dressing site were not eligible
Interventions	Aim: To compare the efficacy of 2 catheter dressing change frequencies (15‐days versus 4‐days) Intervention: Dressing changed every 15 days Control: Dressing changed every 4 days Dressing protocol in both groups: "Three types of dressings were used according to cutaneous toxicity; the adhesive transparent oxygen‐permeable type (Tegaderm) for grade 0 and 1 (48/56; 85% in 15 day group and 32/56; 57% in the 4 day group); the Mefix type for grade 2 and 3 (7/56; 13% in the 15 day group and 23/56; 41% in the 4 day group); and the sterile gauze and tape (American style) dressing (Surgifix, Smith & Nephew, Hull or Velpeau) for grade 4 (1/56; 2% in both the 15 and 4 day groups).  Dressings were changed by the nurse in charge of the patient, under sterile conditions: the dressing was cautiously unstuck, the skin was cleaned with a sterile gauze and Hibidil from the catheter entry point towards the periphery. A sterile gauze was then applied under the dressing. The dressing had to cover the catheter entry point as well as the catheter hub, and the upper limit of the extension line, whatever the dressing type." Duration of follow‐up: Daily surveillance of the dressing and its periphery began on the day of randomisation and was continued throughout hospitalisation Numbers lost to follow‐up: 1 child relapsed in the 15‐day arm before HDC Reason for CVAD insertion: HDC for autologous and allogeneic BMT Method of CVAD insertion: "Catheters were all inserted (subclavian site) in the operating room under strict aseptic conditions.  Physicians wore a cap, a mask, sterile gloves and a gown. The insertion site was first qualitatively cultured and then prepared with 0.5% alcoholic chlorhexidine (Hibidil). The catheters were then inserted cutaneously using the Seldinger technique, and tunnelled subcutaneously up to 10 cm on average in order to allow rapid removal of the material if severe infectious complications were suspected. In the absence of catheter‐related adverse events, the device was left in place until the patient was discharged from the bone marrow transplant unit."  Anatomical location of CVAD: Subclavian site Profession of CVAD inserter: Physician Type of CVAD: Silastic catheters (Vygon) Number of CVAD lumens: Single Dwell time of CVAD: Not stated Study dates: July 1990‐April 1993
Outcomes	Primary outcomes CRBSI: Not included Suspected CRBSI: Blood cultures were taken in the event of fever above 38.5°C and/or signs of local infection All‐cause mortality: Reported mortality with causes Secondary outcomes Catheter‐site infection: Bacteriological samples were taken from skin around the catheter entry point, using plastic agar‐coated slides (Unipath SA, Dardilly, France). All colonies appearing within 48 h of incubation (37°C) were identified by the usual qualitative bacteriological procedures. Catheter entry site cultures were taken in the event of fever above 38.5°C and/or signs of local infection. Skin damage: Skin toxicity at the catheter dressing site and its periphery. Skin toxicity classified as grade 0: healthy skin; grade 1: slightly inflamed skin; grade 2: minor cutaneous lesions, dressing difficult to remove; grade 3: lesions reaching periphery of the dressing; grade 4: cutaneous lesions to such and extent that the usual dressing could no longer be used Pain: Pain during and between dressing changes. Local pain (classified as none, moderate or severe) during the dressing change and between dressing changes Quality of life: Not included Cost: Not included Other outcomes reported in the trial None Inter‐rater reliability: As dressing changes were performed by many different nurses, the skin toxicity grading scale was tested during the 6 months preceding the trial so that the different nursing teams could familiarise themselves with its use Time points: Daily surveillance of the dressing and its periphery began on the day of randomisation and was continued throughout hospitalisation. Whenever the dressing was changed, the grade of skin toxicity was recorded
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Evidence: "Computer‐generated list was used to allocate patients" Comment: Adequate generation of the randomisation sequence
Allocation concealment (selection bias)	Unclear risk	Evidence: Not stated in the trial report Comment: Unable to judge
Blinding of participants and personnel (performance bias) All outcomes	High risk	Evidence: Not stated in the trial report Comment: Not possible to blind the intervention
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Evidence: Not stated Comment: Although it would have been possible to blind outcome assessment, we were unable to ascertain if this was done
Incomplete outcome data (attrition bias) All outcomes	Low risk	Evidence: "One patient relapsed after randomisation and did not receive high dose chemotherapy (15‐day group). The analysis presented here thus concerns 56 patients in each group." Comment: We do not believe that the loss of 1 patient would have affected results
Selective reporting (reporting bias)	Unclear risk	Evidence: All planned outcomes reported Comment: No published protocol. We did not request a copy of the protocol from the trialist
Other bias	High risk	Evidence: Different dressings according to skin damage Comment: Different dressing protocols may have introduced a bias