Table 1.

Overview of outcome measurements of illustrative trials in CLTI patients using gene therapy.

Reference	Vector	Injection site	Patients treated with gene therapy	Diabetic patients	Primary outcome	Secondary outcome	Endpoints met	Study design
Barć et al. (29)	VEGF + HGF enc. PL	IM	14 pIRES/VEGF165/HGF; 14 untreated	All patients	No clear description	ABI, rest pain, angiography	Better wound healing, less rest pain, increased ABI, more collaterals	RNBNP-C
Belch et al. (25)	FGF enc. PL	IM	259 NV1FGF; 266 placebo	52% NV1FGF; 54% placebo	MAFS, study related death <1 year	Mortality, minor amputations, skin lesion status, pain, QOL	None	RDBP-C
Gu et al. (23)	HGF enc. PL	IM	50 low dose; 50 middle dose; 50 high dose; 50 placebo	34–38% per group	Rest pain Ulcer size	TcPO2, ABI, TBI, amputation rate, mortality	Less rest pain, complete ulcer healing*	RDBP-C
Kusumanto et al. (18)	VEGF enc. PL	IM	27 phVEGF165; 27 placebo	All patients	Amputation	ABI, TBI, wound area, pain, mortality	TBI/ABI increased	RDBP-C
Mäkinen et al. (17)	VEGF enc. AV or PL	IA	17 plasmid; 18 adenoviral; 19 placebo	24% PL; 17% AV; 32% placebo	Vascularity (DSA) Major amputation, ulcer healing, rest pain	Restenosis rate, Rutherford class, ABI,	Vascularity increased (DSA)	RDBP-C
Nikol et al. (24)	FGF enc. Pl	IM	59 NV1FGF; 66 placebo	37% NV1FGF; 50% placebo	Ulcer healing	Amputation, mortality, hemodynamic parameters, pain	Amputation risk reduced	RDBP-C
Powell et al. (22)	HGF enc. PL	IM	21 HGF; 6 placebo	62% HGF; 50% placebo	Ulcer healing, major amputation, pain	ABI, TBI, mortality, QOL	TBI improved, pain improved	RDBP-C
Shigematsu et al. (21)	HGF enc. PL	IM	27 HGF; 13 placebo	52% HGF; 62% placebo	Ulcer healing, rest pain	Major amputation, ABI, QOL	Higher improvement rate**	RDBP-C

*in the high-dose group; **not further defined.

ABI, ankle brachial index; AV, adenovirus; enc., encoding; IA, intra-arterial; IM, intramuscular; MAFS, major amputation-free survival; Pl, plasmid; QOL, quality of life; RDBP-C, randomized double-blind placebo-controlled; RNBNP-C, randomized not blinded, not placebo-controlled; TBI, toe brachial index; TcPO₂, transcutaneous oxygen pressure.