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

NCT00420277 | Completed Phase 3 DMC

• 1 other identifier: 6090
• Study Type: interventional
• Target: 462
• Locations: 5 countries
• Sites: 22

Brief Summary

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

Conditions

Hypotension; Ischemia

Keywords

Hip arthroplasty; Anesthesia, spinal; Hypotension; Ischemia; Blood substitutes; Plasma expanders

Outcome Measures

Primary Outcomes (1)

• Total duration of all hypotensive episodes occurring during anesthesia/surgery and throughout the postoperative period (defined as 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 resolve/correct the initial hypotensive episode that led to the first dosing trigger

  Intraoperative

• Time to the second dosing trigger from the first dosing trigger

  Intraoperative

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% HES 130/0.4, 6% hetastarch solution, Voluven

Control

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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

Sponsors & Collaborators

• Sangart: lead

Study Sites (22)

CHU Brugmann

Brussels, Belgium

Location

Z.O.L. Genk

Genk, Belgium

Location

Stedelijk Ziekenhuis Roeselare

Roeselare, Belgium

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, Czechia

Location

Fakultni nemocnice Motol, I. Ortopedicka klinika

Prague, Czechia

Location

Fakultni nemocnice Motol, II. Ortopedicka klinika

Prague, Czechia

Location

Fakultni nemocnice Na Bulovce

Prague, Czechia

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

Tergooi Ziekenhuizen, locatie Hilversum

Hilversum, Netherlands

Location

Sint Maartenskliniek

Nijmegen, Netherlands

Location

UMC Erasmus

Rotterdam, Netherlands

Location

Samodzielny Publiczny Szpital Kliniczny AM

Bialystok, Poland

Location

SP Wojewódzki Szpital Chirurgii Urazowej

Piekary Śląskie, Poland

Location

Wojewódzki Szpital Specjalistyczny nr 5

Sosnowiec, Poland

Location

Instytut Reumatologii, Klinika Reumoortopedii

Warsaw, Poland

Location

SK Dzieciątka Jezus

Warsaw, Poland

Location

Länssjukhuset Gävle

Gävle, Sweden

Location

Kalmar Hospital

Kalmar, Sweden

Location

Lasarettet Motala

Motala, Sweden

Location

Danderyd Sjukhus

Stockholm, Sweden

Location

Söder Hospital

Stockholm, Sweden

Location

Uddevalla Sjukhus

Uddevalla, Sweden

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: 15820947 BACKGROUND

• 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: 15637119 BACKGROUND

• 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: 16096458 BACKGROUND

• 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: 16857991 BACKGROUND

• 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: 16907870 BACKGROUND

• 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: 17122578 BACKGROUND

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

  PMID: 17198847 BACKGROUND

• van der Linden P, Gazdzik TS, Jahoda D, Heylen RJ, Skowronski JC, Pellar D, Kofranek I, Gorecki AZ, Fagrell B, Keipert PE, Hardiman YJ, Levy H; 6090 Study Investigators. A double-blind, randomized, multicenter study of MP4OX for treatment of perioperative hypotension in patients undergoing primary hip arthroplasty under spinal anesthesia. Anesth Analg. 2011 Apr;112(4):759-73. doi: 10.1213/ANE.0b013e31820c7b5f. Epub 2011 Feb 11.

  PMID: 21317165 RESULT

Related Links

• Click here for more information about Sangart, Inc.

MeSH Terms

Conditions

Hypotension; Ischemia

Interventions

maleimide-polyethylene glycol-modified hemoglobin, MP4; HES 130-0.4; Hydroxyethyl Starch Derivatives

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Starch; Dietary Carbohydrates; Carbohydrates; Glucans; Polysaccharides

Study Officials

• Philippe van der Linden, MD, PhD

  CHU Brugmann, Brussels

  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: March 1, 2008
• Study Completion: April 1, 2008
• Last Updated: August 19, 2013

Record last verified: 2013-08

Locations

NL (4); PL (5); SE (6); BE (3); CZ (4)