Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Ipema, 2020

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of  RCTs, comparative studies and case series. Only RCTs are included in current analysis.

Literature search up to November 2018

A: Liistro, 2013

B: Zeller, 2014

C: Zeller, 2015

D: Haddad, 2017

Study design: RCT

Setting and Country:

The Netherlands

Source of funding and conflicts of interest:

CONFLICT OF INTEREST

None.

FUNDING

None

Inclusion criteria SR: Articles were eligible if they included DCB angioplasty or

compared DCB angioplasty with standard PTA of infrapopliteal

arteries in patients with peripheral arterial disease,

were published in English, included human subjects, and had a full text available.

Exclusion criteria SR: case reports,

articles with fewer than 50 infrapopliteal angioplasties, the use of other types of balloons or stents, cutting balloon, cryoplasty, or laser technique, reviews, commentaries, letters to the editor, or conference abstracts.

4 RCTs included

Important patient characteristics at baseline:

N, mean age

A: 132, 74/75y

B: 358, 73/71y

C: 72, 73/70y

D: 93, NR

Sex (% male)

A: 80.3

B: 74.3

C: 79.1

D: NR

Diabetes mellitus

A: 100%

B: 73.5%

C: 66.7%

D: 95.7%

Range of Rutherford category

A: 4-6

B: 3-6

C: 2-5

D: 4-6

A: Liistro

B: Zeller

C: Zeller

D: Haddad

Groups were comparable at baseline

Describe intervention:

A: DCB

B: DCB

C: DCB

D: DCB

Describe  control:

A: PTA

B: PTA

C: PTA

D: PTA

End-point of follow-up:

For review: 12 months

For how many participants were no complete outcome data available?

Numbers specified under outcomes

Restenosis

>50% recurrent stenosis on

duplex ultrasound or angiography, or a peak systolic velocity rate ≥2.5 on duplex ultrasound, at 12 months

A: I: 20/74; C: 55/74

B: I: 25/61; C: 11/31

C: -

D: I: 14/40; C: 34/41

Target lesion revascularization

A clinically driven repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel, at 12 months

A: -

B: I: 27/226; C: 15/111

C: I: 12/40; C: 15/49

D: I: 9/54; C: 29/52

Amputation

Limb salvage (avoidance of major amputation) at 12 months

A: I: 65/65; C: 66/67

B: I: 207/227; C: 107/111

C: I: 29/30; C: 34/36

D: I: 47/48; C: 43/45

Mortality

Overall survival at 12 months

A: I: 60/65; C: 64/67

B: I: 204/227; C: 102/111

C: I: 33/36; C: 34/36

D: I: 38/48; C: 39/48

Quality of life

Not reported

Wound healing

Not reported

Risk of bias (high, some concerns or low):

Tool used by authors: Cochrane tool for assessing risk of bias

A: unclear for blinding outcome assessment, high for blinding participants and personnel

B: unclear for incomplete outcome data and other bias, high for selective reporting and blinding participants and personnel

C: unclear for blinding participants and personnel and for blinding outcome assessment

D: unclear for random sequence generation, allocation concealment, blinding participants and personnel and for blinding outcome assessment

Author’s conclusion

In patients with peripheral arterial disease who underwent infrapopliteal angioplasty, no significant differences in limb salvage, survival, restenosis, TLR, and AFS rates were found when DCB angioplasty was compared with standard PTA.

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Jia, 2020

AcoArt II–BTK

Type of study:

RCT

Setting and country: multicenter, China

Funding and conflicts of interest:

The AcoArt II–BTK study was sponsored by Acotec Scientific.

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Inclusion criteria:

single or sequential de novo or restenotic lesions with >70% diameter stenosis in the infrapopliteal arteries, at least 1 patent runoff vessel to the foot, Rutherford category 4 to 6 ischemia, and a maximum of 2 different arteries to be treated in the same limb.

Exclusion criteria:

Acute thrombosis in the target vessel, planned major amputation of the target limb, history of open surgery of the target vessel, the need for intervention in both limbs at the same time, an existing stenosis or occlusion >150 mm in the inflow vessels (including the iliac artery, superficial femoral artery, and popliteal artery), and in-stent restenosis.

N total at baseline:

Intervention: 61

Control: 59

Important prognostic factors²:

Age, mean ± SD:

I: 70.7±7.4

C: 70.8±9.0

Sex:

I: 59% M

C: 61% M

Diabetes mellitus

I: 45/61 (74)

C: 42/59 (71)

ABI:

I: 0.56±0.27

C: 0.51±0.31

Groups were comparable at baseline.

Angioplasty with Litos or Tulip drug-coated

balloons (DCBs)

The balloons, which

are coated in an inflated state, are covered with 3-μg/mm2 paclitaxel in a matrix containing magnesium stearate as a

polymer-free natural excipient.

Angioplasty with uncoated balloons

The study devices consisted of both the 0.014-inch wire–

compatible Litos and the 0.018-inch–compatible Tulip

series catheters, which are identical in terms of platform, drug material, and coating technology.

Length of follow-up:

12 months

Loss-to-follow-up:

Intervention: 2/61 (3.3%)

Control: 3/59 (5.1%)

Incomplete outcome data:

N/A

Freedom from binary restenosis

Primary patency at 6 months

I: 36/48 patients (75.0)

C: 13/46 patients (28.3)

P<0.001

Re-intervention based on symptomatic restenosis

clinically-driven target lesion revascularization at 6 months

I: 3/65 patients (4.6%)

C: 12/66 patients (18.2%)

clinically-driven target lesion revascularization at 12 months

I: 5/59 (8.5)

C: 13/56 (23.2)

P=0.03

Freedom from CD-TLR at

12-months

I: 91.8% (95% CI 81.9% to 97.3%)

C: 78.0% (95% CI 65.3% to 87.7%)

p=0.028

Amputation

Major amputation at 12 months

I: 1/59 patients (1.7%)

C: 1/56 patients (1.8%)

P=0.97

Wound healing

Complete healing at 12 months

I: 26/31 (83.9%)

C: 24/32 (75.0%)

P=0.39

Quality of life

Not reported

Mortality

One patient (1.7%) died of pneumonia in the DCB group, and 2 patients (3.6%) died of cardiac complications in the control group within 12 months

Authors’ conclusion

This study demonstrated that the Litos/Tulip DCBs are safe and effective in treating infrapopliteal lesions,

with improved angiographic and clinical outcomes vs plain balloon angioplasty. The DCBs demonstrated significantly higher

primary patency with fewer CD-TLRs than conventional angioplasty. The safety of the DCBs was noninferior to that of the

uncoated balloons after 1 year of follow-up.

Liistro, 2020

ACOART-BTK

NCT 02563535

Type of study:

RCT

Setting and country: single center, Italy

Funding and conflicts of interest:

The study was partially supported by Acotec Scientific, which provided the DCBs and covered the costs of angiography core laboratory analysis.

Dr. Liistro is principal investigator of the In.Pact BTK

study for Medtronic; and is a consultant for Medtronic, Boston Scientific, and Biotronik. All other authors have reported that they

have no relationships relevant to the contents of this paper to disclose.

Inclusion criteria:

CLTI (Rutherford class ≥4): stenosis ≥50% or occlusion of at least 40 mm by visual estimation, located in BTK arteries with distal runoff, defined as follows: reconstitution of the occluded or stenotic artery at the level of the malleolus or above with distal direct filling through the dorsalis pedis or plantars of the digital arch (Kawarada classification types 1, 2A, and 2B).

Exclusion criteria:

Patients with absence of pedal arch (Kawarada classification type 3) or those who needed dilatation of the arch to re-establish its patency were excluded.

N total at baseline:

Intervention: 52 patients, 54 limbs, 63 lesions

Control: 53 patients, 55 limbs, 66 lesions

Important prognostic factors²:

Age, mean ± SD:

I: 75.4 ± 8.6

C: 74.80 ± 8.8

Sex:

I: 75% M

C: 77% M

BMI

I: 23.38 ± 3.46

C: 23.31 ± 3.49

Diabetes

I: 52 (100)

C: 49 (93)

ABI:

I: 0.38 ± 0.21

C: 0.37 ± 0.23

Groups were comparable at baseline.

Drug-coated balloon angioplasty

Prior to randomization,

single or sequential balloon dilatations were performed to reach an optimal angiographic result. Balloon diameter was chosen according to vessel diameter measured by extravascular ultrasound (EVUS) with a balloon/artery ratio of 1. In case of DCB angioplasty, a Litos balloon of the same size as the last uncoated balloon was used as previously described. The Litos DCB is coated with paclitaxel.

Plain balloon angioplasty

In case of randomization to POBA, the procedure ended with final angiography.

Length of follow-up:

12 months

Loss-to-follow-up:

I: 3/52

1 consent withdrawal, 2 refused re-angiography

C: 1/53

refused re-angiography

Freedom from binary restenosis

Restenosis >50%

I: 22/58 (37.9%) lesions

C: 54/62 (87.1%) lesions

P <0.001

Re-intervention based on symptomatic restenosis

CDTLR at 12 months

I: 6/62 (10%) lesions

C: 27/66 (41%) lesions

P<0.001

Amputation

Major amputation at 12 months

I: 0

C: 0

Wound healing

complete healing at 12 months

I: 42/47 (89.4%)

C: 35/47 (74.5%)

P=0.05

Quality of life

Not reported

Mortality

12 months

I: 4 (7.7%)

C: 7 (13.2%)

P=0.20

Authors’ conclusion

Litos DCB angioplasty of BTK arteries in patients

with CLTI is associated with significant reductions

in LLL, vessel reocclusion, and TVAL on 6-month

angiography. The higher patency translated into a

lower rate of target lesion revascularization and a

higher rate of complete foot healing, without,

however, a difference in major amputation.

Liistro, 2022

IN.PACT BTK

NCT 02963649

Type of study:

RCT

Setting and country: multicentre, Belgium, France, Greece, Switzerland, Italy

Funding and conflicts of interest:

This study was supported by Medtronic.

F. Liistro is an advisory board member for Biotronik, Boston

Scientific, Medtronic, and Philips. I. Weinberg is a consultant for

Magneto Thrombectomy Solutions, a National Principal Investigator

for Penumbra, Inc., and Medical Director of VASCORE, the

Vascular Imaging Core Laboratory. A. Almonacid Popma receives

no personal fees; her spouse, J. Popma, joined Medtronic as an

employee after completion of the analysis but prior to publication.

M.H. Shishehbor reports consultant income from Abbott Vascular,

Boston Scientific, Medtronic, Philips, and Terumo. S. Deckers is

a full-time employee of Medtronic. A. Micari is an advisory board

member for Boston Scientific and Medtronic.

Inclusion criteria:

Age ≥18 years.

Subject has documented chronic Critical Limb Ischemia (CLI) in the target limb prior to the study procedure with Rutherford Clinical Category 4 or 5. Subjects with documented infection grade 0-2 and ischemia grade 2-3 according to WIfi classification.

Reference Vessel Diameter (RVD) 2 - 4 mm, and confirmed by DUS assessment.

Total occlusions with total lesion length ≥ 40 mm. Lesion must be located in the infrapopliteal arteries and above the ankle joint. Multiple lesions can be treated if located in separate vessels.

…

Exclusion criteria:

Planned index limb amputation above the metatarsal level, or any other planned major surgery within 30 days pre or post-procedure.

Lesion and/or occlusions located or extending in the popliteal artery or below the ankle joint space. Significant inflow lesion or occlusion in the ipsilateral iliac, SFA and popliteal arteries left untreated. Failure to obtain ≤ 30% residual stenosis in pre-existing, hemodynamically significant inflow lesions in the ipsilateral iliac, SFA and popliteal artery.

…

N total at baseline:

Intervention: 23 patients, 25 lesions

Control: 27 patients, 30 lesions

Important prognostic factors²:

Age, mean ± SD:

I: 73.1±7.4

C: 69.6±9.4

Sex:

I: 82.6% M

C: 74.1% M

BMI ≥30 kg/m2

I: 22.7%

C: 26.9%

Diabetes mellitus

I: 73.9 (17/23)

C: 96.3 (26/27)

ABI

Not reported

Groups were comparable at baseline.

Drug coated balloon angioplasty

IN.PACT 014 DCB

Plain balloon angioplasty

Length of follow-up:

9 months

Loss-to-follow-up:

Intervention: 0

Control: 0

Incomplete outcome data:

Specified per outcome

Freedom from binary restenosis

Binary restenosis (≥50%), %

I: 70.0% (14/20 lesions)

C: 83.3% (20/24 lesions)

P=0.472

Re-intervention based on symptomatic restenosis

CD-TLR at 9 months

I: 8.7 (2/23 patients)

C: 8.7 (2/23 patients)

CD-TVR at 9 months

I: 8.7 (2/23 patients)

C: 13.0 (3/23 patients)

Amputation

Major amputation at 9 months

I: 0

C: 0

Wound healing

Not reported

Quality of life

Not reported

Mortality

I: 4.3 (1/23)

C: 8.0 (2/25)

Authors’ conclusion

At nine months, participants in the DCB group experienced a large separation (53% lower) in subsegmental LLL compared to those in the PTA group. Similarly, using the classic method, participants in the DCB group showed a trend of lower LLL compared to those in the PTA group. Safety outcomes were similar between the two arms.

Liistro, 2022

DEBATE-BTK

NCT 01556542

Type of study:

RCT

Setting and country: single-centre, Italy

Funding and conflicts of interest:

This study was not supported by any funding.

Dr. Francesco Liistro has the following relation to disclose within the last 2 years: Consultant for Medtronic, Boston scientific and Biotronic. The authors declare that they have no conflict of interest.

Inclusion criteria:

Presence of diabetes mellitus, CLI (Rutherford class 4 or greater), stenosis or occlusion ≥40 mm of at least 1 tibial vessel with distal runoff to the foot, and agreement to 12-month angiographic evaluation.

Exclusion criteria:

life expectancy <1 year, allergy to paclitaxel, contraindication to combined antiplatelet treatment, and planned major amputation before angiography

N total at baseline:

Intervention: 65

Control: 67

Important prognostic factors²:

Age, mean ± SD:

I: 74 ± 9.4

C: 75 ± 9.6

Sex:

I: 83% M

C: 78% M

Diabetes mellitus

100%

ABI

I: 0.31 ± 0.8

C: 0.29 ± 1.0

Groups were comparable at baseline.

Drug coated balloon angioplasty

IN.PACT balloon

Plain balloon angioplasty

Length of follow-up:

5 years

Loss-to-follow-up:

Not specified

Incomplete outcome data:

Not specified

Freedom from binary restenosis

Not specified for this time point

Re-intervention based on symptomatic restenosis

CD-TLR at 5 years, per lesion

I: 29 (37%)

C: 36 (46%)

Amputation

Major amputation at 5 years

I: 1/65 (2%)

C: 2/67 (3%)

Wound healing

Not reported

Quality of life

Not reported

Mortality

I: 24/65 (36.9)

C: 32/67 (46.3)

Authors’ conclusion

Overall survival at 5-year was similar in DCB treated patients compared to POBA. Moreover, survival

was higher in patients that received DCB angioplasty at

any time of the 5 years period.

Patel, 2021

SINGA-PACLI Trial

NCT 02129634

Type of study:

RCT

Setting and country: two-center, Singapore.

Funding and conflicts of interest:

Supported by the National Medical Research Council (NMRC).

One author disclosed payment for lectures from

Boston Scientific. disclosed money to author’s institution for grant from the National Medical Research Council Singapore; support for travel from

Singapore Health Services. One author disclosed research grant from the National Medical Research Council Singapore.

Inclusion criteria:

21 years or older; Rutherford category 4, 5, or 6; stenosis of 50% or

more (at visual angiographic assessment) or occlusion of at least

one native infrapopliteal artery; there had to be a posttreatment expectation

of at least one patent vessel to the ankle

Exclusion criteria:

The total lesion length was not

to exceed 200 mm.

N total at baseline:

Intervention: 70

Control: 68

Important prognostic factors²:

Age, mean ± SD:

I: 61 ± 10

C: 64 ± 10

Sex:

I: 61% M

C: 74% M

Diabetes mellitus

I: 94%

C: 94%

ABI

I: 0.80 ± 0.30

C: 0.80 ± 0.28

Groups were comparable at baseline.

Drug-coated balloon angioplasty

(Passeo-18 Lux; Biotronik)

Non-coated balloon angioplasty

(Passeo-18; Biotronik)

Length of follow-up:

12 months

Loss-to-follow-up:

Intervention: 15/70 (21%)

1 withdrew consent

14 defaulted clinical follow-up

Control: 7/68 (10%)

2 withdrew consent

5 defaulted clinical follow-up

Incomplete outcome data:

Not specified

Freedom from binary restenosis

Primary patency of target lesion at 6 months:

I: 30/70 (43%)

C: 26/68 (38%)

Re-intervention based on symptomatic restenosis

CD-TLR at 12 months

I: 8/41 (20%)

C: 10/53 (19%)

Amputation

Major amputation at 12 months

I: 17/68 (25%)

C: 10/65 (15%)

Wound healing

Complete healing of index wound

I: 35/67 (52%)

C: 39/67 (61%)

Quality of life

Not reported

Mortality

I: 15/70 (21%)

C: 11/68 (16%)

Authors’ conclusion

Our randomized controlled trial demonstrated

that drug-coated balloon angioplasty not only did not

improve primary patency of the below-the-knee arteries in patients with critical limb ischemia compared with percutaneous transluminal angioplasty at 6 months, but also resulted in shorter amputation-free survival or in another term higher amputation rate after 12 months.

Bosiers, 2012

DESTINY

NTC 00510393

Type of study:

RCT

Setting and country: multicenter, Europe

Funding and conflicts of interest:

This trial was funded by Abbott Laboratories.

Competition of interest: Drs Bosiers, Scheinert, and Zeller serve on the Advisory Board of Abbott Vascular. Dr Schwartz is a full-time employee of Abbott Laboratories.

Inclusion criteria:

chronic symptomatic peripheral arterial disease (PAD) in Rutherford-Becker clinical categories 4 to 5 (ischemic rest pain or ischemic ulceration) due to atherosclerotic de novo occlusive lesions of the tibial arteries. symptomatic PAD due to a maximum of two focal de novo atherosclerotic target lesions in one or more infrapopliteal vessels. Lesions with ≥50% diameter stenosis were considered for the trial when their length was

≤40 mm and they arose in target vessels with diameters of 2.0 to 3.5 mm.

Exclusion criteria:

Not specified.

N total at baseline:

Intervention: 74 patients, 78 lesions, 86 stents

Control: 66 patients, 76 lesions, 92 stents

Important prognostic factors²:

Age, mean ± SD:

I: 75 ± 8.0

C: 76 ± 8.4

Sex (%male):

I: 61

C: 67

Diabetes mellitus

I: 60%

C: 50%

ABI

Not reported

Groups were comparable at baseline.

Everolimus-eluting stent

Xience V everolimus-eluting stent with Multi-Link Vision stent platform

Bare metal stent

Multi-Link Vision stent.

Length of follow-up:

12 months

Loss-to-follow-up:

12-month angiographic follow-up 46%.

Reasons: death in 23, refusal in 21, excessive risk due to medical comorbidity in 14, poor image quality precluding reliable interpretation by the core laboratory in 14, loss to clinical follow-up in seven, and major extremity amputation in three.

The frequency of angiographic follow-up was equal between

the two groups (Vision 46% vs Xience V 49%; P = 0.73).

Incomplete outcome data:

Not specified

Freedom for binary restenosis

Restenosis ≥50% at 12 months

I: 17%, 13/75

C: 36%, 26/73

Freedom from restenosis

I: 83%, 62/75

C: 64%, 47/73

Primary patency

At 12 months

I: 85.2%

C: 54.4%

Patency per lesion, but numbers not possible to deduce. Number of patients not specified.

Re-intervention based on symptomatic restenosis

freedom from target lesion revascularization

I: 92% 78/85

C: 65% 76/117

Amputation

Major amputation

I: 1/74

C: 2/66

Wound healing

Not reported

Quality of life

Not reported

Mortality

I: 18%, 13/74

C: 16% 11/66

Authors’ conclusion

The results

showed that after 12 months, use of the Xience V DES significantly decreased late lumen loss, restenosis, and the need for repeat intervention. These data suggest that Xience V stenting is a useful therapeutic adjunct in patients with CLI that require prolonged patency following endovascular recanalization.

Spreen, 2016

NCT 00471289

PADI trial

Type of study:

RCT

Setting and country: multi-center, the Netherlands

Funding and conflicts of interest:

The PADI trial received an unrestricted grant during the conduct of

the study from The Netherlands Society for Interventional Radiology,

who had no role in study design, data collection, analysis, interpretation,

or writing of the report.

Dr Overhagen has received speaker’s fees from Cordis Corporation,

Fremont, CA; Cook Medical, Bloomington, IN; and AngioDynamics,

Latham, NY. The above are unrelated to the submitted work. The other

authors report no conflicts.

Inclusion criteria:

Adult patients were eligible for enrollment if they have CLI (defined as Rutherford category ≥4) caused by infrapopliteal lesions. Lesions were considered for inclusion if there was >50% luminal loss, lesion length of ≤90 mm, and reference vessel diameter 2 to 6 mm, estimated by pretreatment imaging.18 Inflow had to be unobstructed, possibly after revascularization in the femoropopliteal segment during the same session. Outflow distal to target lesions should consist of ≥1 crural vessel with expected unobstructed runoff until the level of the ankle joint.

Exclusion criteria:

In data supplement

N total at baseline:

Intervention: 73 patients, 74 limbs

Control: 64 patients, 66 limbs

Important prognostic factors²:

For example

age (SD):

I: 74.2 (12.1)

C: 72.9 (11.9)

Sex:

I: 67.1% M

C: 73.4% M

Diabetes:

I: 60.3%

C: 67.2%

Groups were comparable at baseline.

Drug-eluting stent

In the DES arm, target lesions were treated with balloon expandable

paclitaxel-eluting stainless steel coronary stents (TAXUS Liberté; Boston Scientific, Natick, MA). If necessary, according to the

operator, mainly in cases of occlusion, lesions were predilated.

Bare-metal stent

Patients in the PTA±BMS arm received PTA according to the normal practice of the operator. A balloon with a diameter matching the target vessel was advanced over the guidewire and inflated at the target lesion site.

Length of follow-up:

12 months

Loss-to-follow-up:

Intervention:

7 patients incomplete follow-up for imaging

Control:

6 patients incomplete follow-up for imaging

Incomplete outcome data:

Not specified

Freedom from binary restenosis

Less than 50% stenosis at 6 months

I: 48%, 47/98 lesions

C: 35.1%, 27/77 lesions

Re-intervention based on symptomatic restenosis

At 6 months

I: 3/73 patients, 4.1%

C: 0/64

Amputation

Major amputation at 12 months

I: 8/74 limbs

C: 13/66 limbs

Wound healing

Not reported

Quality of life

Not reported

Mortality

At 12 months

I: 17/73 patients

C: 16/64 patients

Authors’ conclusion

In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS.

Spreen, 2017

Follow-up to Spreen, 2016

Length of follow-up:

5 years

Freedom from binary restenosis

≤50% stenotic at 2 years

I: 15/48, 31.3%

C: 11/45, 24.4%

At 5 years

I: 5/43, 11.6%

C: 3/35, 8.6%

Re-intervention

Total number not reported

Amputation

Major amputation at 2 years

I: 9/68, 13.2%

C: 15/60, 24.8%

At 5 years

I: 11/57, 19.3%

C: 17/50, 34%

Wound healing

Not reported

Quality of life

Not reported

Mortality

At 2 years

I: 17/73, 23.3%

C: 19/64, 29.7%

At 5 years

I: 32/73, 43.8%

C: 31/64, 48.8%

Authors’ conclusion

this randomized controlled trial showed that

long-term amputation- and event-free survival in patients with

CLI due to infrapopliteal lesions is more favorable after

treatment with DESs compared with the conventional endovascular

strategy of PTA-BMS. The limited available morphological

results also showed higher preserved patency rates after DESs

than after PTA-BMS. Given the feasibility of DESs for

infrapopliteal lesions, proven not only at short and midterm

but also long term, one should consider treatment with a DES

in patients with CLI caused by lesions below the knee.

Study reference

(first author, publication year)

Was the allocation sequence adequately generated?

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

LOW

Some concerns

HIGH

Fanelli, 2014

Definitely yes;

Reason: Patients were randomized (1:1) without stratification using computer-generated assignments when they entered the angiographic suite.

Probably yes;

Reason: not specified

Probably no;

Reason: health care providers were not blinded, but patients and outcome assessors were blinded.

Definitely yes;

Reason: No loss to follow-up reported.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for CD-TLR

Jia, 2020

Definitely yes;

Reason: All patients were randomly assigned to the DCB or control group (1:1 ratio) by a central randomization computer system.

Definitely yes;

Reason: Opaque, sealed envelopes were used and opened by an independent researcher.

Definitely no;

Reason: No specific measures were taken to blind the person who performed the repeat angiography or who made the decision about CD-TLR,

whereas quantitative evaluation of the angiograms was performed by a core laboratory blinded to the type of treatment

provided.

Definitely yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for CD-TLR

Liistro, 2020

Definitely yes;

Reason: Target lesions were randomly assigned to 1 of the 2

study arms after optimal angioplasty. Randomization

was performed in 2 parallel blocks of 10 with the use

of computer-generated random digits.

Probably yes;

Reason: Prior to randomization,

single or sequential balloon dilatations were performed to reach an optimal angiographic result. In case of randomization to POBA, the procedure ended with

final angiography.

Definitely no;

Reason: patients were blinded, but health care providers were not. Outcomes of interest are not likely affected by lack of blinding, except CD-TLR

Definitely yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for CD-TLR

Liistro, 2022

IN.PACT BTK

Probably yes;

Reason: mentioned but not specified.

Probably yes;

Reason: mentioned but not specified.

Definitely no;

Due to the nature of the procedure, it

was not possible to blind the operator or study site staff. In addition, participants were not blinded due to inherent differences in procedure between the DCB and PTA groups

Definitely yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for CD-TLR

Liistro, 2022

DEBATE-BTK

Definitely yes;

Lesions were randomly assigned to 1 of the 2 study arms after successful passage of the guidewire. Randomization was performed in blocks of 10 with the use of computer-generated random digits.

Definitely yes;

Group assignments were placed in sealed envelopes.

Definitely no;

The study was not blinded.

No information

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for CD-TLR

Patel, 2021

SINGA-PACLI

Definitely yes;

The randomization sequence was computer generated by our academic collaborator (Singapore Clinical Research Institute), with permuted block lengths of four and six, and stratification by diabetes mellitus, end-stage renal failure status, and study site.

Definitely yes;

To conceal treatment allocation, we used tamper-proof serially numbered opaque envelopes accessible only to the operator performing the procedure.

Definitely no;

Participants and study personnel who performed the follow-up imaging (duplex US and angiography) assessments were blinded to the treatment assignment. Clinicians deciding revascularization were not blinded.

Probably no;

For later time points, loss to follow-up was considerable and different between intervention and control group (20 vs 10%)

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for CD-TLR and outcomes at 12 months

Bosiers, 2020

DESTINY

Definitely yes;

Block randomization and stratification per center were conducted using block sizes of

eight, which resulted in slightly unequal study populations.

Definitely yes;

After successful wire traversal, patients were randomized 1:1 using preprovided sealed envelopes.

Definitely no;

Patients were blinded to their treatment assignment,

and study site personnel were counseled on

nondisclosure. The physician performing the procedure

was not blinded to the assigned treatment.

Probably no;

Loss to follow-up up to one year was limited for clinical outcomes, but high for outcomes based on imaging.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for CD-TLR and patency at 12 months

Falkowski, 2008

Definitely yes;

Patients were

randomly divided into two groups using statistica StatSoft

No information

Definitely no;

Open-label study

Probably yes;

Loss to follow-up up was infrequent

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for CD-TLR

Rastan, 2011

Rastan, 2021

Definitely yes;

We allocated patients to the two treatment groups using a computer-generated

random sequence, set in blocks for each participating

centre. Patients were randomly assigned to the groups in a 1:1 ratio.

Probably yes;

Not specified, but likely.

Definitely yes;

Physicians and patients

were unaware of the treatment-group assignment. All clinical endpoints were adjudicated

by an independent clinical-events committee. All physicians including

the medical staffs, the research coordinators, and the clinical-events

committee were blinded for the treatment-group assignments.

Probably no;

Loss to follow-up up was limited for clinical outcomes, but high for outcomes based on imaging.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for patency

Spreen, 2016

Spreen, 2017

PADI

Definitely yes;

Computer-generated random sequence on a 1:1 basis. andomization was per limb and

stratified in blocks per center.

Definitely yes;

The attending radiological technician

opened the sealed, opaque envelope.

The block size (n=4) was known only

to the statistician.

Definitely no;

Patients, operators, and investigators were not blinded

Probably yes;

Reason: Loss to follow-up up was infrequent

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for CD-TLR