NCT00421200

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
375

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Feb 2007

Shorter than P25 for phase_3

Geographic Reach
6 countries

18 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 9, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 11, 2007

Completed
21 days until next milestone

Study Start

First participant enrolled

February 1, 2007

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2008

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2008

Completed
Last Updated

August 19, 2013

Status Verified

August 1, 2013

Enrollment Period

1.2 years

First QC Date

January 9, 2007

Last Update Submit

August 15, 2013

Conditions

HypotensionIschemia

Keywords

Hip arthroplastyAnesthesia, spinalHypotensionIschemiaBlood substitutesPlasma expanders

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (10)

  • 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

  • +5 more secondary outcomes

Study Arms (2)

Hemospan (MP4OX)

EXPERIMENTAL

4.3 g/dL MalPEG-Hb solution

Drug: Hemospan (MP4OX)

Control

ACTIVE COMPARATOR

Voluven (HES 130/0.4)

Drug: Voluven (HES 130/0.4)

Interventions

Hemospan (MP4OX)DRUG

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

Also known as: MP4OX solution, 4.3 g/dL MalPEG-Hb, PEGylated Hb
Hemospan (MP4OX)
Voluven (HES 130/0.4)DRUG

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

Also known as: 6% hetastarch solution, 6% HES 130/0.4
Control

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Univ. Ziekenhuis Antwerp

Antwerp, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

ZOL Campus Sint-Jan

Genk, Belgium

Location

AZ St. Lucas Hospital

Ghent, Belgium

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, Czechia

Location

Oblastni nemocnice Kladno

Kladno, Czechia

Location

Fakultni nemocnice Motol

Prague, Czechia

Location

Fakultni nemocnice Na Bulovce

Prague, Czechia

Location

Sint Maartenskliniek

Nijmegen, Netherlands

Location

Universitair Medisch Centrum St. Radboud

Nijmegen, Netherlands

Location

SPSK nr 4, Klinika Ortopedii, Traumatologii i Rehabilitacji AM

Lublin, Poland

Location

SP Wojewódzki Szpital Chirurgii Urazowej

Piekary Śląskie, Poland

Location

Wojewódzki Szpital Specjalistyczny nr 5

Sosnowiec, Poland

Location

SK Dzieciątka Jezus

Warsaw, Poland

Location

Skaraborg Hospital

Skövde, Sweden

Location

Karolinska Hospital

Stockholm, Sweden

Location

S:t Görans Hospital

Stockholm, Sweden

Location

Univ. Hospital - Queen's Medical Center

Nottingham, United Kingdom

Location

Related Publications (8)

  • 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.

    PMID: 15820947BACKGROUND

  • Cabrales P, Tsai AG, Winslow RM, Intaglietta M. Effects of extreme hemodilution with hemoglobin-based O2 carriers on microvascular pressure. Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2146-53. doi: 10.1152/ajpheart.00749.2004. Epub 2005 Jan 6.

    PMID: 15637119BACKGROUND

  • Young MA, Riddez L, Kjellstrom BT, Bursell J, Winslow F, Lohman J, Winslow RM. MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine. Crit Care Med. 2005 Aug;33(8):1794-804. doi: 10.1097/01.ccm.0000172648.55309.13.

    PMID: 16096458BACKGROUND

  • Tsai AG, Cabrales P, Manjula BN, Acharya SA, Winslow RM, Intaglietta M. Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers. Blood. 2006 Nov 15;108(10):3603-10. doi: 10.1182/blood-2006-02-005272. Epub 2006 Jul 20.

    PMID: 16857991BACKGROUND

  • Winslow RM. Current status of oxygen carriers ('blood substitutes'): 2006. Vox Sang. 2006 Aug;91(2):102-10. doi: 10.1111/j.1423-0410.2006.00789.x.

    PMID: 16907870BACKGROUND

  • 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.

    PMID: 17122578BACKGROUND

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

    PMID: 17198847BACKGROUND

  • Olofsson CI, Gorecki AZ, Dirksen R, Kofranek I, Majewski JA, Mazurkiewicz T, Jahoda D, Fagrell B, Keipert PE, Hardiman YJ, Levy H; Study 6084 Clinical Investigators. Evaluation of MP4OX for prevention of perioperative hypotension in patients undergoing primary hip arthroplasty with spinal anesthesia: a randomized, double-blind, multicenter study. Anesthesiology. 2011 May;114(5):1048-63. doi: 10.1097/ALN.0b013e318215e198.

    PMID: 21455059RESULT

Related Links

MeSH Terms

Conditions

HypotensionIschemia

Interventions

maleimide-polyethylene glycol-modified hemoglobin, MP4HES 130-0.4Hydroxyethyl Starch Derivatives

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

StarchDietary CarbohydratesCarbohydratesGlucansPolysaccharides

Study Officials

  • Christina I. Olofsson, MD, PhD

    Karolinska University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 9, 2007

First Posted

January 11, 2007

Study Start

February 1, 2007

Primary Completion

May 1, 2008

Study Completion

June 1, 2008

Last Updated

August 19, 2013

Record last verified: 2013-08

Locations

GB(1)NL(2)BE(4)PL(4)CZ(4)SE(3)