Phase III Study of Hemospan® for Treating Hypotension in Hip Arthroplasty

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sangart
ClinicalTrials.gov Identifier:
NCT00420277
First received: January 9, 2007
Last updated: August 15, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to determine whether Hemospan is superior to Voluven for treatment of 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 Intervention Phase
Hypotension
Ischemia
Drug: Hemospan (MP4OX)
Drug: Voluven (HES 130/0.4)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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® toTreat Hypotension in Patients Undergoing Primary Hip Arthroplasty With Spinal Anesthesia

Resource links provided by NLM:


Further study details as provided by Sangart:

Primary Outcome Measures:
  • Total duration of all hypotensive episodes occurring during anesthesia/surgery and throughout the postoperative period (defined as the first 6 hours following skin closure) [ Time Frame: Up to 6 hours after skin closure ] [ Designated as safety issue: No ]

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 [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Mortality (In-hospital, and all-cause at 30 days) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Time to resolve/correct the initial hypotensive episode that led to the first dosing trigger [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]
  • Time to the second dosing trigger from the first dosing trigger [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]
  • Proportion of patients treated successfully with one dose [ Time Frame: Intraoperative ] [ Designated as safety issue: No ]
  • Incidence of hypotension [ Time Frame: Up to 6 hours after skin closure ] [ Designated as safety issue: No ]
  • Duration of the longest period of hypotension recorded [ Time Frame: Up to 6 hours after skin closure ] [ Designated as safety issue: No ]
  • Incidence of intervention with a pressor agent to treat hypotensive episodes [ Time Frame: Up to 6 hours after skin closure ] [ Designated as safety issue: No ]
  • Incidence of postoperative intervention with a diuretic for volume-overload or inadequate urine output [ Time Frame: Post-operative day 3 ] [ Designated as safety issue: No ]

Enrollment: 462
Study Start Date: February 2007
Study Completion Date: April 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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% HES 130/0.4
  • 6% hetastarch solution
  • Voluven

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 treating 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 and treating hypotension in orthopedic surgery patients undergoing hip replacement surgery under spinal anesthesia.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00420277

Locations
Belgium
CHU Brugmann
Brussels, Belgium
Z.O.L. Genk
Genk, Belgium
Stedelijk Ziekenhuis Roeselare
Roeselare, Belgium
Czech Republic
Fakultni nemocnice Hradec Kralove
Hradec Kralove, Czech Republic
Fakultni nemocnice Motol, I. Ortopedicka klinika
Prague, Czech Republic
Fakultni nemocnice Na Bulovce
Prague, Czech Republic
Fakultni nemocnice Motol, II. Ortopedicka klinika
Prague, Czech Republic
Netherlands
Medisch Spectrum Twente
Enschede, Netherlands
Tergooi Ziekenhuizen, locatie Hilversum
Hilversum, Netherlands
Sint Maartenskliniek
Nijmegen, Netherlands
UMC Erasmus
Rotterdam, Netherlands
Poland
Samodzielny Publiczny Szpital Kliniczny AM
Bialystok, Poland
SP Wojewódzki Szpital Chirurgii Urazowej
Piekary Śląskie, Poland
Wojewódzki Szpital Specjalistyczny nr 5
Sosnowiec, Poland
SK Dzieciątka Jezus
Warsaw, Poland
Instytut Reumatologii, Klinika Reumoortopedii
Warsaw, Poland
Sweden
Länssjukhuset Gävle
Gävle, Sweden
Kalmar Hospital
Kalmar, Sweden
Lasarettet Motala
Motala, Sweden
Danderyd Sjukhus
Stockholm, Sweden
Söder Hospital
Stockholm, Sweden
Uddevalla Sjukhus
Uddevalla, Sweden
Sponsors and Collaborators
Sangart
Investigators
Principal Investigator: Philippe van der Linden, MD, PhD CHU Brugmann, Brussels
  More Information

Additional Information:
Publications:

Responsible Party: Sangart
ClinicalTrials.gov Identifier: NCT00420277     History of Changes
Other Study ID Numbers: 6090
Study First Received: January 9, 2007
Last Updated: August 15, 2013
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Czech Republic: State Institute for Drug Control
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sangart:
Hip arthroplasty
Anesthesia, spinal
Hypotension
Ischemia
Blood substitutes
Plasma expanders

Additional relevant MeSH terms:
Hypotension
Ischemia
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Hetastarch
Plasma Substitutes
Blood Substitutes
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014