Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT00500669 |
| Other study ID # |
H0011 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 3
|
| First received |
July 12, 2007 |
| Last updated |
April 10, 2017 |
| Start date |
June 2004 |
| Est. completion date |
December 2013 |
Study information
| Verified date |
April 2017 |
| Source |
Royal Hobart Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
To investigate whether Betadine can reduce infection rates and recurrence rates following
varicose veins surgery in a randomized double blind placebo controlled study.
Description:
Introduction. Varicose vein surgery is common. Worldwide, the commonest indication for this
type of surgery is cosmesis. However, there are also some medical indications, including
venous eczema, lipodermatosclerosis and venous ulceration. The surgery is usually straight
forward and can in most instances be done as a day case. Patient and medical practitioner
expectations are therefore high. Surgery in the groin is notorious for its risk of wound
infection. In primary varicose vein surgery, the groin wound infection can rate can be as
high as 20% 1. A more realistic figure might be approximately 10% (Sains PS, Reddy KM, Jones
HJS and Derodra JK. Audit of varicose vein surgery: the patients perspective. Phlebology
2005 20(4) 179 - 182.)
A small prospective study has been conducted at the Royal Hobart Hospital to establish the
wound infection rate in this hospital. All procedures were performed under the care of a
single surgeon who routinely soaks the groin wound in Betadine. Patients were followed up on
a weekly basis for six weeks and had wound inspections by an independent nurse consultant.
Of the 11 patients (five female, mean age 50.3years, range 31 - 74 years, mean weight 92kg,
range 60 - 130kg, mean body mass index 41) who have now completed six weeks of follow up,
there were a total of 17 groin wounds. Only one of these (6%) has had an infection.
Unfortunately, this study was terminated prematurely as the independent nurse who was
performing the wound assessments has been replaced and there was a lag interval of at least
6 weeks before her replacement was due to start.
One of the major problems with varicose vein surgery is the risk of recurrence. Recurrent
varicose veins are more difficult to deal with than primary varicose veins and thus every
effort must be made at the time of the primary surgery to perform an operation with the
lowest recurrence rate. Despite adequate surgery, recurrence can develop via
neovascularisation in the groin. This may be part of the normal wound healing process. If
neovascularisation can be prevented, this may reduce the recurrence rate. However, this
should not be at the detriment of healing of the groin wound.
Previous in vitro studies have looked at the effect of povidone-iodine on some of the
components of wound healing. It can be toxic to granulocytes, monocytes and keratinocytes 2,
3 . Dilute Povidone-Iodine solutions are also known to inhibit human skin fibroblast growth
in vitro 4, 5. In vivo studies, however, have failed to show any clinically significant
delay in wound healing when wounds are irrigated with povidine iodine 4.
Povidine-iodine has bacteriocidal effects 6. Could it be that those groin wounds which
develop an infection develop neovascularisation as part of the inflammatory response?
Topical antimicrobial agents are commonly used in wound management. This is based on the
premise that reduction of bacterial contamination aids wound healing. Sindelar showed that
the incidence of superficial infections of surgical wounds irrigated with povidone-iodine
solution prior to closure was less than wounds irrigated with saline (2.9% vs. 15.1%) 7 .
No toxicity has been reported with povidone-iodine used as a brief rinse or soak, as planned
for this study.
In order to assess the effect of Betadine (10% povidone-iodine) in the groin wound on
infection rates and recurrence rates in patients undergoing primary varicose vein surgery we
will conduct a prospective, randomized study.
Following injury and haemostasis, hypoxia, high lactate levels and acidosis stimulate
angiogenesis. Under the influence of factors such as bFGF and VEGF, endothelial cells
proliferate and form capillary buds. These cells secrete matrix metalloproteases which allow
vascular buds to dissect through the wound matrix while EGF and PDGF recruit pericytes which
stabilise the new vessel formation (Betsholtz C, Lindblom P, Gerhardt H. Role of pericytes
in vascular morphogenesis. EXS9422005; 115 - 125
Investigators. Mr. S. R. Walker - Staff Specialist, Vascular Surgery. Prof. Sinha -
Associate Professor of Surgery Mr. David Cottier - Visiting Medical Officer - Vascular
Surgery.
Protocol. Inclusion criteria - Patients undergoing primary saphenofemoral ligation for
varicose veins (can be combined with short saphenous surgery).
Exclusion criteria - Allergy to iodine Redo groin dissections Patients having multiple
avulsions only or saphenopopliteal ligation only Patients unable to return to outpatients
for 6 weeks to undergo assessment with the wound care nurse
Patients admitted under the care of Prof. Sinha or Mr. S. R. Walker are to be included.
Patients suitable for the study will be recruited from the outpatient department. If the
patient agrees to be included in the study, they should undergo a pre-operative venous
duplex scan. This may alter the operative plan. If patients have had a duplex scan prior to
a decision on surgery, this scan does not need to be repeated.
On admission for surgery the patient should undergo the usual pre-operative work up,
including weight and height. Their past medical history should be recorded.
All patients should receive a pre-operative dose of low molecular weight heparin (Clexane
20mg) as thromboembolic prophylaxis. The groin area is shaved immediately before the
operation. The groin and legs are prepared for surgery in the usual way using aqueous
Betadine. No prophylactic antibiotics are to be given. The surgical procedure in the groin
is then performed in a standard manner to expose the saphenofemoral junction. The junction
and all tributaries are ligated. In all cases the long saphenous vein should be pin stripped
to the level of the knee.
At this point, patients are randomized via a sealed envelope to either a saline soaked gauze
or a Betadine soaked gauze placed in the groin wound. This is left in place for a minimum of
one minute. Some surgeons may then chose to close the groin wound before proceeding to the
avulsions while others may choose to leave the soaked swab in place while any avulsions are
dealt with. The length of time the swab is left in the groin wound should be recorded.
The groin wound is then closed with vicral to the fascia and monocryl to the skin. The groin
wound is dressed with a non occlusive dressing.
Post operative protocol - Patients will be booked to see the wound care consultant on a
weekly basis for 6 weeks. The patients will be booked into Prof. Sinha and Mr. Walker's
outpatient clinic on Thursday morning. The wound care consultant will attend these clinics
to assess the wounds. The wound care consultant will be blinded as to whether saline or
Betadine was used in the groin. The wounds will be classified as:
1. - normal post operative wound, no signs of infection
2. - erythema of the wound not extending for more than 5mm from wound edge
3. - erythema more than 5mm but no wound discharge
4. - discharge of pus from wound
5. - wound dehiscence with infection, presence of pus and necrotic tissue.
At the six week follow up, the patient should undergo a venous duplex scan. This scan is
performed to ensure an adequate surgical procedure has been performed.
One year following the surgical procedure, patients undergo a final venous duplex scan to
assess for signs or recurrence, and in particular, a recurrence in the groin.
Both post operative duplex request forms should be completed at the time of the original
operation with dates on the request forms for the scans.
End points. Primary end point - groin wound infection Secondary end point - groin recurrence
of varicose veins
Statistics. If use of Betadine can reduce the infection rate (from 20%) and recurrence rate
by 50%, for a study with 90% power, we would require at least 100 patients in each group.
This number could be more readily recruited in a multicentre study.
It is envisaged that approximate
