Clinical Trials

Study 6034 – Phase II Limb Ischemia (Sweden)

Details
This single-blind, phase II pilot study was conducted at the Karolinska Hospital in Stockholm, Sweden. The primary objective was to investigate the effect of MP4OX on vascular resistance by evaluating blood flow in the forearm (non-invasive strain-gauge plethysmography) and cardiac output (noninvasive inert gas mixture re-breathing technique) in patients with chronic critical leg ischemia (CCLI). The secondary objective was to evaluate the effects of MP4OX on local skin blood flow (laser Doppler flow probes) and tissue oxygenation (transcutaneous PO2 electrodes) in a severely ischemic region of the foot. Adult male or female (surgically sterile or post-menopausal) patients with CCLI that met the following criteria were enrolled: history of pain at rest and/or ulceration; ankle systolic blood pressure (BP)/brachial systolic BP index (ABI) <0.6 at the time of inclusion; and ankle systolic BP <70 mmHg and/or toe systolic BP <50 mmHg. [Additional details about the protocol can be found at http://clinicaltrials.gov/ct/show/NCT00633659]

Two dose cohorts were planned (250 mL or 500 mL; with N = 4 MP4OX and 2 Voluven controls per dose group). After completing the 6 patients in the 250-mL cohort, a decision was made to stop enrollment since the primary study objective was reached, and due to technical issues with the stability of the secondary efficacy parameters (regional blood flow and tissue oxygenation measurements). No patients were enrolled into the 500 mL cohort because it was decided that further collection of these data in a second dose cohort would likely not provide superior data.

Results

Vital signs: Despite some increase in blood pressures, there was no increase in vascular resistance in the MP4OX group, suggesting that the blood pressure changes were likely secondary to rapid volume expansion from the hyperoncotic colloid properties of MP4OX in patients with noncompliant vasculature due to advanced vascular disease.

Blood flow and tissue oxygenation findings: Blood flow and pressure changes in the forearm demonstrated no evidence of increased vascular resistance following MP4OX administration. There were no measurable changes observed in the ischemic limb in laser Doppler flow values, and no improvement in transcutaneous PO2 values recorded in either group.

Adverse events: There were no severe AEs, deaths, or AEs leading to discontinuation in this study. There was 1 SAE of severe lower limb ischemia with troponin elevation that was considered by the investigator unlikely to be related to investigational product, and resolved within 3 days. All AEs were deemed to be unlikely to be related to investigational product, and all non-serious AEs resolved in approximately 1 day.

Laboratory findings: Overall, the hematology and chemistry findings for this study were unremarkable; mild, transient changes from baseline were considered not clinically relevant.