ILOFLOW: The Arterial Measurement of the Blood Flow Volume After Iloprost Stimulation

Sponsor

Prim PD Dr Afshin Assadian (Other)

Overall Status

Unknown status

CT.gov ID

NCT01774058

Collaborator

Wilhelminenspital Vienna (Other)

100

Enrollment

Location

Arm

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A prospective case-control study was performed to investigate the effect of iloprost on the intraoperative flow volume in diabetic and non-diabetic patients as well as the effect of peripheral neuropathy in patients with peripheral arterial occlusive disease (PAOD) undergoing arterial reconstruction (primary endpoint).

100 patients undergoing femoral artery reconstruction or femorodistal bypass surgery were included. Prior to surgery, peripheral nerve conduction velocity was measured. Blood flow volume at the common femoral artery was assessed using a Doppler flowmeter (Sono TT FlowLab; ) before reconstruction, prior to the intraarterial application of 3000ng of iloprost and 5 and 10 minutes afterwards. Peripheral resistance units (PRU) were calculated as a function of mean systemic arterial pressure (MAP) and flow volume (VF): PRU = MAP (mmHg) / VF (ml/min).

Condition or Disease	Intervention/Treatment	Phase
Diabetes Arteriosclerosis Peripheral Arterial Occlusive Disease Neuropathy	Drug: Ilomedin	Phase 2

Detailed Description

The therapeutic properties of prostanoids appear to be primarily due to its vasodilative effect. However, the inhibition of platelet aggregation with a limitation of thrombus formation and the inhibition of the adhesion of leucocytes to endothelial lesions also help to improve blood flow in the peripheral circulation .

It is currently unclear which effects of prostanoids are predominant for diabetic patients. The present study was performed to assess potential differences of iloprost efficiency for patients with or without type II diabetes mellitus with or without peripheral neuropathy.

The study was a single center, controlled, non- randomized interventional study. All patients provided their written consent. The study has been approved by the Ethics Committee of the city of Vienna in 2012 (EC nr: 11-144-0512) and was extended annually for the last two years. Performance of the study complied with the World Medical Association Declaration of Helsinki regarding ethical conduct of research involving human subjects.

The study was designed to enroll 100 consecutive patients with peripheral arterial occlusive disease undergoing surgical reconstruction of the inguinal arteries and/or femorodistal bypass surgery. Indication for surgery included PAOD Fontaine stage IIb (waking distance less than 200 meters), III (rest pain) or IV (tissue loss). Surgical procedures were planned and the absence of inflow stenoses verified based on MRI or CT angiography. Exclusion criteria for participation in the study comprised contraindications for the application of iloprost as well as a planned spinal anesthesia. Patients were divided into two groups based on being diabetic type II or non-diabetic. Before surgery measurement of nerve conduction velocity was performed by a trained nurse at the Department of Physiotherapy in order to determine the presence of neuropathy.

Surgery was performed under general anesthesia via a longitudinal skin incision. After systemic administration of 5000 IU of unfractionated Heparin, the peripheral vessels were clamped. After longitudinal arteriotomy, thrombendarterectomy of the common femoral artery was performed in all cases, extending into the deep femoral artery and superficial femoral artery when necessary. In some cases, this was followed by femoropopliteal bypass surgery. Provided the systolic blood pressure was equal to or above 100 mmHg at the end of the reconstruction, 3000 ng of iloprost (Ilomedin), diluted in 15ml saline solution, were injected into the common femoral artery. Distal to the injection site doppler flow measurement was performed at the common femoral artery prior to arteriotomy, prior to the intraarterial application of iloprost, 5 and 10 minutes afterwards, using the Sono TT FlowLab instrument (em-Tec GmbH, Munich). Transmission heads were selected to fit tightly around the reconstructed vessel without producing a stenosis. During the procedure, systemic arterial blood pressure was continuously documented using a pressure transducer connected to an intraarterial cannula placed in the radial artery of the forearm. The result of the arterial reconstruction was routinely checked by intraoperative on- table angiography. Before discharge from the hospital the surgical reconstruction was controlled by duplex ultrasound as well as an assessment of the ankle brachial index.

Statistical analysis was performed with SPSS 15.0 for Windows (SPSS Inc, Chicago, Ill). To correct all measurements of flow volume for blood pressure, peripheral resistance units (PRU) were calculated as a function of mean systemic arterial pressure (MAP) and flow volume (VF): PRU = MAP (mmHg) / VF (ml/min).

The patient population was stratified by the presence of diabetes and by the presence of peripheral neuropathy in the operated limb. Kolmogorov-Smirnov testing confirmed normal distribution of all continuous variables. Descriptive statistics (mean, standard deviation, range) were applied to acquired data, and tests for dependent or independent variables were used for comparison of continuous variables, as applicable. Categorical variables were expressed as frequencies and percentages, and differences between groups were investigated by the Pearson Chi -square and Fisher exact tests. Patient characteristics potentially modulating the effect of iloprost were investigated by linear regression analysis. P values < 0.05 were considered significant.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Intraoperative Arterial Measurement of the Blood Flow Volume After Iloprost Stimulation in Diabetics and Non-diabetics: Implication for Outcome-prediction and Perioperative Therapy

Study Start Date :

Oct 1, 2012

Anticipated Primary Completion Date :

Jun 1, 2019

Anticipated Study Completion Date :

Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ilomedin, bloodflow volume, measurement, Surgery was performed under general anesthesia via a longitudinal skin incision. After systemic administration of 5000 IU of unfractionated Heparin, the peripheral vessels were clamped. Following a longitudinal arteriotomy, thrombendarterectomy of the common femoral artery was performed in all cases, extending into the deep femoral artery and superficial femoral artery when necessary. At the end of the reconstruction, 3000 ng of iloprost (Ilomedin), diluted in 15ml saline solution, were administered into the common femoral artery. Distal to the injection site doppler flow measurement was performed at the common femoral artery prior to arteriotomy, prior to the intraarterial application of iloprost and 5 and 10 minutes afterwards, using the Sono TT FlowLab instrument. During the procedure, systemic arterial blood pressure was continuously documented using a pressure transducer connected to an intraarterial cannula placed in the radial artery of the forearm.	Drug: Ilomedin 3000ng ilomedin in 15ml salt water will be injected intraarterial into the common femoral artery over 2 minutes for one time,then the investigators will measure the blood flow volume after 5 and then after 10 minutes on the common femoral artery. The patients will be observed by the anaesthesiologist. The patient will get ilomedin one day before the surgery and then for 6 day after surgery into the vein. (10microgramm/o,5ml in 250ml salt water) Other Names: Product Code 1-22460 ATC Code: B01AC11 concentrate and solvent for injection

Arm

Intervention/Treatment

Experimental: Ilomedin, bloodflow volume, measurement,

Drug: Ilomedin

3000ng ilomedin in 15ml salt water will be injected intraarterial into the common femoral artery over 2 minutes for one time,then the investigators will measure the blood flow volume after 5 and then after 10 minutes on the common femoral artery. The patients will be observed by the anaesthesiologist. The patient will get ilomedin one day before the surgery and then for 6 day after surgery into the vein. (10microgramm/o,5ml in 250ml salt water)

Other Names:

Product Code 1-22460

ATC Code: B01AC11

concentrate and solvent for injection

Outcome Measures

Primary Outcome Measures

The measurement of the blood flow volume is done with the Sono TT FlowLab (em-Tec GmbH, Munich) ultrasound instrument on the common femoral artery in diabetics and non-diabetics after ilomedin administration. [6 weeks after surgery]
Before surgery reconstruction the first measurement with the Sono TT FlowLab (em-Tec GmbH, Munich) ultrasound instrument will be done on the common femoral artery and then after surgery reconstruction. Therefore there will be different measuring heads exactly fitting around the vessels. Then the administration of 3000ng Ilomedin® in 15ml saline will be injected into the common femoral artery via a a cannula over two minutes if the systolic blood pressure of the patient is over 100mm Hg. The blood flow volume will be measured again after five and ten minutes on the same point. Those results will be documented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients with diabetes and non diabetes
patients with peripheral artery occlusive disease and who undergo surgical treatment in distal vessels
spinal anesthesia
written consent