Condition category
Surgery
Date applied
29/09/2006
Date assigned
29/09/2006
Last edited
20/04/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Mr Kevin Varty

ORCID ID

Contact details

Box 201
Dept of Surgery
Addenbrooke's NHS Trust
Cambridge
CB2 2QQ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N0544170118

Study information

Scientific title

An Investigation into the role of Matrix Metalloproteinases (MMPs) in Lower Limb Vascular Restenosis

Acronym

Study hypothesis

Does blocking enzymes in the wall of the artery - matrix metalloproteinases (MMPs) - prevent the artery from narrowing after angioplasty (balloon treatment) or surgery (bypass graft)?

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Surgery: Cardiovascular

Intervention

Patients under the care of the Cambridge Vascular Unit undergoing femoro-popliteal angioplasty or femoro-popliteal/tibial bypass will be eligible for the study. The indication for intervention will be severe limb ischaemia (rest pain, ulceration, gangrene) or short distance claudication failing to respond to medical and exercise therapy.

Pre-procedural Noninvasive Assessments:
Following informed consent the degree of ischaemia will be measured using ankle brachial pressure index (ABPI) measurements and transcutaneous oxygen measurements (TcPO2). Arterial stiffness and Endothelial Function will also be determined by applying a pressure probe to the carotid and radial arteries in turn with concomitant ECG gating.

Percutaneous Angioplasty:
These procedures are routinely carried out as either day cases or with overnight stay. During the procedure two 40 ml blood samples will be taken for plasma MMP analysis, plus CRP level, cholesterol, U&Es, elastin breakdown products, elastase activity and genetic analyses. One 40 ml sample will be systemic venous blood taken from the venous access cannula inserted for the procedure. A second 40 ml sample will be taken from the femoral vein in the leg undergoing the procedure. This is blood returning from the treated leg, and is more likely to reflect the local MMP activity potentially related to restenosis. On the same day as the PTA procedure the patients will be commenced on the SDD/placebo medication in a double blind randomised design. One tablet (25 mgs SDD) twice per day. This will be continued for 24 weeks post procedure.

Post Procedure Follow Up:
Colour duplex ultrasound assessment of the angioplasty site will be used to document blood velocities across the lesion and percentage of restenosis. These measurement will take place in the Vascular Laboratory at the following intervals: 1, 6, 12, 24, 36, 52 weeks. At 24 and 52 weeks repeat blood samples will be taken.

Femoro-distal bypass:
The same pre-procedural assessments will be performed as for PTA. These assessments will be co-ordinated with the patients pre-clerking clinic visit, usually 1 week prior to surgery. During surgery 2 tissue samples will be taken. One will be an arterial wall biopsy, to be analysed for arterial tissue MMP status. This will be taken from the proximal anastomosis site as a small ellipse avoiding any stenosis/narrowing of the anastomosis. A second sample will be taken from the venous tissue used for the bypass for MMP analysis.

As soon as patients are taking oral medication post operatively (usually 12-24 hours) the SDD/placebo medication will be commenced. As for PTA this will be for 24 weeks.

Prior to discharge the graft will be scanned to establish baseline graft velocities and any early abnormalities. As with the PTA protocol, further graft monitoring for stenosis, ABPI, and TcPO2 measurements will occur at 6, 12 , 24, 36 and 52 weeks. Surveillance of vein grafts at these intervals is normal clinical practice. Blood samples will be taken at 24 and 52 weeks.

Intervention type

Mixed

Phase

Drug names

Primary outcome measures

1. MMP activities SDD versus placebo
2. CRP levels
3. Endothelial function and re-stenosis
4. Arterial wall stiffness and re-stenosis.

Secondary outcome measures

Not provided at time of registration

Overall trial start date

18/07/2005

Overall trial end date

18/07/2008

Reason abandoned

Eligibility

Participant inclusion criteria

Serum samples collected at the time of vascular intervention (radiologist or surgeon). Follow up samples by vascular research fellow.

Arterial wall and vein biopsies taken at the time of surgery by operating surgeon.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

35 in each trial arm, ie 270

Participant exclusion criteria

1. Patient unable to give informed consent
2. Age < 18 years
3. Pregnancy, planned pregnancy
4. Life expectancy less than 12 months
5. Inability to monitor the angioplasty site or graft with ultrasound for stenosis
6. Unable to take SDD (ie allergic reaction) or currently taking tetracyclines
7. Unable to take adjuvant treatment with antiplatelet/anticoagulant agent and statin

Recruitment start date

18/07/2005

Recruitment end date

18/07/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Addenbrooke's NHS Trust
Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Organisation

Record Provided by the NHSTCT Register - 2006 Update - Department of Health

Sponsor details

The Department of Health
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk

Sponsor type

Government

Website

http://www.dh.gov.uk/Home/fs/en

Funders

Funder type

Government

Funder name

Cambridge Consortium - Addenbrooke's (UK), NHS R&D Support Funding

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes