Increasing Dose Safety Study of Hemospan in Orthopedic Surgery Patients

Hypotension Clinical Trial

Official title:

A Clinical Safety (Phase Ib/II) Increasing Dose Study of MP4 (Hemospan) in Orthopedic Surgery Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00494949
• Other study ID #: 3002
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 28, 2007
• Last updated: August 15, 2013
• Start date: April 2003
• Est. completion date: August 2006

Study information

• Verified date: August 2013
• Source: Sangart
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and possible effectiveness of Hemospan solution in patients undergoing elective orthopedic surgery who receive spinal anesthesia.

Description:

Allogeneic (donor) blood transfusions are often required during and/or after orthopedic hip surgery to maintain adequate hemoglobin concentration, prevent tissue ischemia, treat hypotension, and compensate for fluid shifts. For example, during hospitalization for hip replacement, patients may receive up to two to three units of blood. This amount varies depending on the technical difficulty of the surgery, the patient's hemoglobin concentration prior to surgery, and the patient's clinical status.

The limited availability, logistic constraints and documented risks associated with allogeneic blood transfusions have prompted the search for alternative therapies. Autologous (self-donated) red blood cell pre-donation can be used in many cases but age, anemia and co-morbidities often preclude the use of this treatment. Cell saving and re-infusion also prevents blood transfusion, but this practice also has potential problems and limited applicability.

Over the past 75 years various "blood substitutes" have been developed for potential clinical use. To date all have shown significant toxicity in preclinical or clinical studies and regulatory approval of these synthetic or hemoglobin-based products has been impeded by safety concerns.

Hemospan is a novel polyethylene-modified hemoglobin solution specifically developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. As a result of the molecular size and oxygen dissociation characteristics, Hemospan selectively off-loads oxygen in tissues predisposed to low oxygen tension. In preclinical studies Hemospan has been found to be free of significant toxicity in a variety of animal species in doses exceeding those that will be used in this study.

In the Phase I safety study in normal volunteers, Hemospan was well tolerated in doses up to 100 mg/kg (approximately 200 mL of a 4g/dL Hemospan solution).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2006
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult male or postmenopausal female(last menses at least 12 months prior and laboratory assessment verifying appropriate FSH and LH levels [laboratory assessments not necessary if last menses at least 12 months prior]), American Society of Anesthesiologists classification system (ASA) class I or II patients over the age of 18 scheduled for orthopedic surgery with spinal anesthesia

• Patients have to be in good health (other than the orthopedic indication for surgery) as determined by medical history, physical examination, clinical laboratory studies and ECG, all within four weeks prior to drug administration

• At screening (within four weeks prior to drug administration) the iohexol clearance, urinalysis and hematology (hemoglobin, hematocrit, RBC, WBC, platelets, reticulocytes percentage), PT, PTT had to be within the laboratory normal limits, If a clinical laboratory value (Na, K, albumin, serum creatinine, urea, bilirubin, AST, ALT, ALP, GGT, LDH, conjugated bilirubin, lipase, amylase, total protein, C1, Ca, CK, CK-MB, troponin, cholesterol, glucose, ß-2 microglobulin, NAG, osmolarity) is outside the normal range the laboratory test can be repeated. A patient with two consecutive abnormal values is not allowed to participate in the study unless the PI determines the change is not clinically significant. A notation of "Not clinically significant (NCS)" is noted on the laboratory record in that case.

• Patients have to sign an informed consent form for the study, which is reviewed and approved by the IECs of the Karolinska Hospital or the Stockholm Söder Hospital

Exclusion Criteria:

• Any acute or chronic condition which limits the patient's ability to complete the study or jeopardizes the safety of the patient

• Patients with a history, or clinical manifestation of significant metabolic disorders, cardiovascular disorders (including arrhythmia, tachycardia, hypertension, angina pectoris, chronic heart failure) or psychiatric disorders

• Patients with a history of chronic hepatic or renal disease

• Pregnancy

• Patients who have received any other investigational drugs within 30 days prior to administration of the study drug

• Patients who test positive to human immunodeficiency virus (HIV), hepatitis B or hepatitis C screens or have any other chronic infection

• Professional or ancillary personnel involved with the study

• Presence of a hemoglobinopathy

• Known allergy to iodine-containing intravenous contrast material or seafood

• Coagulopathy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypotension
• Hypoxia

Intervention

Drug:
• Hemospan (MP4OX)
200, 400, 600, 750, or 1000 mL of Hemospan (MP4OX)
• Ringer's lactate
200, 400, 600, 750, or 1000 mL of Ringer's lactate solution

Locations

Country	Name	City	State
Sweden	Department of Orthopedics, Karolinska Hospital	Stockholm
Sweden	Department of Orthopedics, Stockholm Söder Hospital	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Sangart

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

Björkholm 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. — View Citation

Olofsson C, Ahl T, Johansson T, Larsson S, Nellgård 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 — View Citation

Winslow RM. Red cell substitutes. Semin Hematol. 2007 Jan;44(1):51-9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events		21 days	Yes
Secondary	Changes from baseline in pulse oximetry		4 days	No
Secondary	Change in Arterial blood gas and blood lactate levels from baseline		4 days	No
Secondary	Duration of supplemental inspired oxygen [FIO2]		4 days	No
Secondary	Number and duration of intra-operative hypotensive episodes (SBP<90 mmHg or a DBP <50 mmHg)		4 days	No
Secondary	Incidence of pharmacologic intervention for hypotension		4 days	No
Secondary	Volume blood products administered		4 days	No
Secondary	Change from baseline in vital signs		4 days	No
Secondary	Changes in serum chemistry and hematology from baseline		4 days	No
Secondary	Volume of IV fluids given		4 days	No

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