Phase III Study of Hemospan® to Prevent Hypotension in Hip Arthroplasty

Sponsor

Sangart (Industry)

Overall Status

Completed

CT.gov ID

NCT00421200

Collaborator

(none)

375

Enrollment

Locations

Arms

Duration (Months)

20.8

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Hemospan is superior to Voluven for preventing hypotensive episodes during the perioperative period (from induction of spinal anesthesia until 6 hours after skin closure), and for reducing the incidence of operative and postoperative complications including organ dysfunction and failure until follow-up at one month following surgery. An independent Data Safety Monitoring Board (DSMB) will periodically evaluate the safety data collected during this trial.

Condition or Disease	Intervention/Treatment	Phase
Hypotension Ischemia	Drug: Hemospan (MP4OX) Drug: Voluven (HES 130/0.4)	Phase 3

Detailed Description

Hemospan is a novel hemoglobin-based oxygen carrier developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. As a result 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 rapid and effective plasma expansion and tissue perfusion, and that the properties of Hemospan target oxygen release in the microcirculation.

Spinal anesthesia is the preferred choice for hip arthroplasty procedures in elderly patients, but is associated with a functional hypovolemia due to loss of vascular tone that frequently causes acute hypotensive episodes. Hypotension represents a surrogate marker of hypovolemia that may be further exacerbated by surgical bleeding, which can result in decreased cardiac output, insufficient perfusion and inadequate tissue oxygenation. Ischemia resulting from hypotension can adversely affect vital organ function and may result in complications and postoperative morbidity. As the population ages and more patients become candidates for orthopedic reconstruction or joint replacement surgery, the number of patients at risk is increasing. The ideal IV solution for preventing hypovolemia-associated hypotension and improving hemodynamic stability would be an effective plasma expander that promotes tissue perfusion and delivers oxygen to ischemic or marginally hypoxic tissue.

Preclinical animal studies have shown that Hemospan may be well-suited to this application and may even be better than blood in some situations. Data from Sangart's Phase II orthopedic surgery study (No. 6055), published recently by Olofsson et al. (Anesthesiology 2006; 105(6): 1153-63) support the safety and potential benefit of Hemospan for preventing hypotension in orthopedic surgery patients undergoing hip replacement surgery under spinal anesthesia.

Study Design

Study Type:

Interventional

Actual Enrollment :

375 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Phase III Study of the Efficacy and Safety of an Oxygen-carrying Plasma Expander, Hemospan®, Compared With Voluven® to Prevent Hypotension in Patients Undergoing Primary Hip Arthroplasty With Spinal Anesthesia

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

May 1, 2008

Actual Study Completion Date :

Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hemospan (MP4OX) 4.3 g/dL MalPEG-Hb solution	Drug: Hemospan (MP4OX) 250 ml unit dose, up to 500 mL total dose, as needed at protocol-defined dosing triggers Other Names: MP4OX solution 4.3 g/dL MalPEG-Hb PEGylated Hb
Active Comparator: Control Voluven (HES 130/0.4)	Drug: Voluven (HES 130/0.4) 250 ml unit dose, up to 500 mL total dose, as needed at protocol-defined dosing triggers Other Names: 6% hetastarch solution 6% HES 130/0.4

Arm

Intervention/Treatment

Experimental: Hemospan (MP4OX)

4.3 g/dL MalPEG-Hb solution

Drug: Hemospan (MP4OX)

250 ml unit dose, up to 500 mL total dose, as needed at protocol-defined dosing triggers

Other Names:

MP4OX solution

4.3 g/dL MalPEG-Hb

PEGylated Hb

Active Comparator: Control

Voluven (HES 130/0.4)

Drug: Voluven (HES 130/0.4)

250 ml unit dose, up to 500 mL total dose, as needed at protocol-defined dosing triggers

Other Names:

6% hetastarch solution

6% HES 130/0.4

Outcome Measures

Primary Outcome Measures

Proportion of patients who develop at least one hypotensive episode during anesthesia/surgery and throughout the postoperative period (the first 6 hours following skin closure) [Up to 6 hours after skin closure]

Secondary Outcome Measures

Incidence of serious operative and postoperative complications, combined into a Composite Morbidity Outcome that includes acute heart failure, acute MI, ischemic stroke, and renal failure [30 days]
Incidence of operative and postoperative organ dysfunction related to ischemia and/or tissue hypoxia, as a Composite Ischemia Outcome that includes clinical evidence of cerebral ischemia, myocardial ischemia, and renal dysfunction [30 days]
Mortality (in-hospital, and all-cause at 30 days) [30 days]
Time to the first hypotensive episode (SBP < 90 mmHg or < 75% of BL) following completion of the dosing regimen [Intraoperative]
Time to administration of the second dose [Intraoperative]
Proportion of patients that only receive/require one dose and avoid hypotension [Up to 6 hours after skin closure]
Total duration of all hypotensive episodes [Up to 6 hours after skin closure]
Duration of the longest period of hypotension recorded [Up to 6 hours after skin closure]
Incidence of intervention with a pressor agent to treat hypotension [Up to 6 hours after skin closure]
Incidence of postoperative intervention with a diuretic for volume-overload or inadequate urine output [Post-operative day 3]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients scheduled to undergo elective primary hip arthroplasty (based on an osteoarthritis diagnosis) under spinal anesthesia
Adult male or female (surgically sterile or post-menopausal), aged 50 years or older
American Society of Anesthesiology (ASA) Class II or III
Physical examination, laboratory status, vital signs, and ECG within acceptable limits for the planned surgery, as judged by the investigator
Have been given written and verbal information by the investigator about Hemospan and the protocol, and have had the opportunity to ask questions about the study
Patients must sign an Informed Consent form that has been reviewed and approved by the independent Ethics Committee

Exclusion Criteria:

Hip fracture patients and nail/pin extraction procedures
Clinical evidence of uncontrolled cardiovascular, infectious, psychiatric, metabolic or systemic disorders including diabetes and rheumatoid arthritis
Evidence of significant hypertension with SBP >180 mmHg, or a difference in SBP obtained in each arm that is >15 mmHg (measured in the supine position in both arms, at screening)
Recent history or evidence of MI or stroke (within 6 months)
Known alcohol or drug dependency
Currently taking oral anti-coagulant therapy; except for low-dose aspirin (acetylsalicylic acid), <200 mg/day
History of coagulopathy
Involved in any investigational drug or device trial within 30 days prior to this study
Professional or ancillary personnel involved with this study

Contacts and Locations

Locations

	Site	City	Country
1	Univ. Ziekenhuis Antwerp	Antwerp	Belgium
2	Cliniques Universitaires Saint-Luc	Brussels	Belgium
3	ZOL Campus Sint-Jan	Genk	Belgium
4	AZ St. Lucas Hospital	Ghent	Belgium
5	Fakultni nemocnice Hradec Kralove	Hradec Kralove	Czech Republic
6	Oblastni nemocnice Kladno	Kladno	Czech Republic
7	Fakultni nemocnice Motol	Prague	Czech Republic
8	Fakultni nemocnice Na Bulovce	Prague	Czech Republic
9	Sint Maartenskliniek	Nijmegen	Netherlands
10	Universitair Medisch Centrum St. Radboud	Nijmegen	Netherlands
11	SPSK nr 4, Klinika Ortopedii, Traumatologii i Rehabilitacji AM	Lublin	Poland
12	SP Wojewódzki Szpital Chirurgii Urazowej	Piekary Śląskie	Poland
13	Wojewódzki Szpital Specjalistyczny nr 5	Sosnowiec	Poland
14	SK Dzieciątka Jezus	Warsaw	Poland
15	Skaraborg Hospital	Skövde	Sweden
16	Karolinska Hospital	Stockholm	Sweden
17	S:t Görans Hospital	Stockholm	Sweden
18	Univ. Hospital - Queen's Medical Center	Nottingham	United Kingdom