Santema

The addition of hyperbaric oxygen did not importantly improve ulcer healing or reduce major amputation rate in patients with diabetic foot ulcers.

Clinical bottom line:

1. No statistically significant improvement in ulcer healing with HBOT 2. No significant improvement in major amputation with HBO

Citation/s:1. Santema KT, Stoekenbroek RM, Koelemay MJ, Reekers JA, van Dortmont LM, Oomen A, Smeets L, Wever JJ, Legemate DA, Ubbink DT. Hyperbaric Oxygen Therapy in the Treatment of Ischemic Lower-Extremity Ulcers in Patients With Diabetes: Results of the DAMO2CLES Multicenter Randomized Clinical Trial. Diabetes care. 2018 Jan 1;41(1):112-9
Lead author's name and fax: Dirk T. Ubbink, d.ubbink@ amc.nl.

Three-part Clinical Question:For patients with ischaemic diabetic foot ulcer, does the addition of hyperbaric oxygen to standard care, result in an increased proportion with healed ulcer?
Search Terms: Diabetic foot ulcer; problem wound; ischaemia

The Study:Non-blinded randomised controlled trial with intention-to-treat.
The Study Patients: Diabetic adults with foot ulcer Wagner Grade 2 to 4 present for at least four weeks and with limb ischaemia shown by ABI or PtcO2.
Control group (N = 60; 58 analysed): Revascularisation if required, antibiotics, good control and anticoagulants as indicated, and standard wound care according to an international working group recommendation.
Experimental group (N = 60; 57 analysed): As above plus 100% oxygen breathing at 2.4 ATA for 90 minutes daily Monday to Friday to healing or a maximum of 40 sessions.

The Evidence:

Outcome	Time to Outcome	Control group	HBO group	Relative risk reduction	Absolute risk reduction	NNT
Major amputation	1 year	0.22	0.112	46%	0.10	10
	95% CIs:			-15% to 100%	-0.03 to 0.23	NNT = 4 to INF; NNH = 31 to INF
Healed wound	1 year	0.48	0.55	14.6%	0.07	15
	95% CIs:			-23% to 51%	-0.11 to 0.25	NNT = 4 to INF; NNH = 9 to INF
Alive and free of major amputation	1 year	0.68	0.82	20%	0.14	7
	95% CIs:			-2% to 42%	-0.02 to 0.29	NNT = 3 to INF; NNH = 64 to INF

Comments:
1. Power calculation suggested 226 patients required to find a 12% higher rate of healing. This study suggests a 10% difference but is underpowered. Likely Type II error.
2. Per-protocol analysis suggested significantly lower amputation rate with HBOT (22% v 5%)
3. No significant difference found in time to healing using survival analysis.
4. 32% of patients in both groups had ulcer recurrence during follow-up.
5. Two patients had HBO-related adverse events - oxygen toxic seizure (1) and perforated tympanic membrane (1). Both recovered.
6. It is unusual to recruit and randomise patients before ensuring they are fit for treatment as happened here to four patients allocated to HBOT.
7. 52% of participants had Wagner Grade 2 ulcers - commonly not seen as an indication for HBOT, and a higher proportion of HBO group patients had Wagner Grade 3 and 4 ulcers (42% v 55%). Both these factors are likely to bias toward the null.

Appraised by:Mike Bennett m.bennett@unsw.edu.au ; Friday, 18 September 2020
Kill or Update By: September 2022