Pilot Study of Hemospan® in Patients With Chronic Critical Limb Ischemia

NCT ID: NCT00633659

Last Updated: 2013-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2008-12-31

Brief Summary

The purpose of this study is to evaluate the effects of Hemospan infusion on vascular reactivity, regional perfusion and oxygenation of ischemic tissue in patients with chronic critical lower limb ischemia.

Detailed Description

Hemospan® is a novel hemoglobin-based oxygen carrier developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. Because of its molecular size and oxygen binding characteristics, Hemospan selectively off-loads oxygen in tissues predisposed to low oxygen tension. Preclinical evidence suggests that Hemospan provides volume expansion and enhances tissue perfusion. Hemospan is therefore being developed as an oxygen-carrying plasma expander for patients where tissues are at risk of inadequate perfusion and oxygenation.

In patients with chronic critical lower limb ischemia (CCLI), the primary cause of ischemic symptoms in the leg is insufficient perfusion. As many of the patients suffering from CCLI are elderly and have concomitant disease, surgical procedures may not always be possible. The goal of all treatments is to improve the blood flow in the nutritional vessels of the ischemic areas; one such possibility may be to use an oxygen-carrying plasma expander.

Hemospan has been shown to improve the oxygenation of tissues by preserving functional capillary density. In addition, Hemospan has a high affinity for oxygen - a feature that is specifically designed to target the unloading of oxygen in the microcirculation where local PO2 levels are much lower (e.g., in ischemic regions). Since Hemospan is a cell-free oxygen carrier, it should be able to perfuse capillaries that are so constricted that red blood cells are unable to flow through them.

Conditions

Vascular Disease; Critical Lower Limb Ischemia

Keywords

Hemospan; Oxygen carriers; Blood substitutes; Ischemia; Tissue oxygenation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Hemospan (MP4OX)

4.3 g/dL MalPEG-Hb solution

Group Type: EXPERIMENTAL

Hemospan (MP4OX)

Intervention Type: DRUG

250 mL of Hemospan (MP4OX)

Control

Voluven (HES 130/0.4)

Group Type: EXPERIMENTAL

Voluven (HES 130/0.4)

Intervention Type: DRUG

250 mL of Voluven (HES 130/0.4) solution

Interventions

Hemospan (MP4OX)

250 mL of Hemospan (MP4OX)

Intervention Type: DRUG

Voluven (HES 130/0.4)

250 mL of Voluven (HES 130/0.4) solution

Intervention Type: DRUG

Other Intervention Names

MP4OX solution; 4.3 g/dL MalPEG-Hb; PEGylated Hb; 6% hetastarch solution; 6% HES 130/0.4

Eligibility Criteria

Inclusion Criteria

• Adult male or female (surgically sterile or post-menopausal) patients with CCLI that meet the following definition: i) History of pain at rest and/or ulceration; ii) Ankle systolic BP/Brachial systolic BP Index (ABI) <0.6 at the time of inclusion; iii) Ankle systolic BP <70 mmHg and/or toe systolic BP <50 mmHg
• Has received written and verbal information about the investigational product and the protocol by the investigator and has had the opportunity to ask questions about the study
• Patients must sign an Informed Consent Form (ICF), that has been reviewed and approved by the independent Ethics Committee (EC)

Exclusion Criteria

• Severe congestive heart failure (EF <40%, or New York Heart Association Class III or IV
• Any acute or chronic condition that will limit the patient's ability to complete the study
• Recent acute coronary syndrome (unstable angina or myocardial infarction [MI] within 1 month)
• Severe dementia or clinically significant psychiatric disorder requiring active treatment
• Evidence of untreated or uncontrolled hypertension (SBP >180 mmHg, or DBP >100 mmHg), or a difference in systolic BP in each arm that is >15 mmHg (measured by cuff and a pen-Doppler at screening in the supine position, in both arms)
• Smoking or use of any nicotine-containing product (e.g., snuff) within previous 24 hours before start of study
• Any systemic rheumatic disease
• Taking oral steroid therapy (does not include steroids taken intermittently via inhaler)
• Chronic hepatic disease (abnormal LFTs >3X upper limit of normal, known history of Hepatitis C or B)
• Chronic renal disease (creatinine >1.8 mg/dL, or known polycystic kidney disease)
• Expectation of poor patient compliance with study protocol
• Patients scheduled for surgical procedure within 7 days from start of this study
• Involved in any investigational drug or device trial within 30 days prior to this study
• Professional or ancillary personnel involved with this study

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sangart

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pär Olofsson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

Karolinska Universitetssjukhuset

Stockholm, , Sweden

Countries

Sweden

References

Bjorkholm M, Fagrell B, Przybelski R, Winslow N, Young M, Winslow RM. A phase I single blind clinical trial of a new oxygen transport agent (MP4), human hemoglobin modified with maleimide-activated polyethylene glycol. Haematologica. 2005 Apr;90(4):505-15.

Reference Type: BACKGROUND

PMID: 15820947 (View on PubMed)

Olofsson C, Ahl T, Johansson T, Larsson S, Nellgard P, Ponzer S, Fagrell B, Przybelski R, Keipert P, Winslow N, Winslow RM. A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery. Anesthesiology. 2006 Dec;105(6):1153-63. doi: 10.1097/00000542-200612000-00015.

Reference Type: BACKGROUND

PMID: 17122578 (View on PubMed)

Olofsson C, Nygards EB, Ponzer S, Fagrell B, Przybelski R, Keipert PE, Winslow N, Winslow RM. A randomized, single-blind, increasing dose safety trial of an oxygen-carrying plasma expander (Hemospan) administered to orthopaedic surgery patients with spinal anaesthesia. Transfus Med. 2008 Feb;18(1):28-39. doi: 10.1111/j.1365-3148.2007.00811.x.

Reference Type: BACKGROUND

PMID: 18279190 (View on PubMed)

Winslow RM. Red cell substitutes. Semin Hematol. 2007 Jan;44(1):51-9. doi: 10.1053/j.seminhematol.2006.09.013.

Reference Type: BACKGROUND

PMID: 17198847 (View on PubMed)

Related Links

http://sangart.com

For more information about Sangart, Inc.

Other Identifiers

6034

Identifier Type: -

Identifier Source: org_study_id