HypotensionPhase 1/2NCT00494949
Increasing Dose Safety Study of Hemospan in Orthopedic Surgery Patients
A Phase 1/2 study testing Hemospan (MP4OX) and Ringer's lactate in people with Hypotension and Hypoxia, run by Sangart at 2 sites in Sweden.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypotension, Hypoxia
- What is being tested?
- Hemospan (MP4OX) and Ringer's lactate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesSweden
- Study dates
- Apr 2003to Aug 2006
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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, β-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
Who cannot join
- 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
Show all 10Show fewer
- Professional or ancillary personnel involved with the study
- Presence of a hemoglobinopathy
- Known allergy to iodine-containing intravenous contrast material or seafood
- Coagulopathy
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Department of Orthopedics, Karolinska Hospital
Stockholm, SE-171 76
Department of Orthopedics, Stockholm Söder Hospital
Stockholm, SE-171 76
About this study
Official title: A Clinical Safety (Phase Ib/II) Increasing Dose Study of MP4 (Hemospan) in Orthopedic Surgery Patients
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.
Read the detailed 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).
- Conditions
- Hypotension, Hypoxia
- Being tested
- Hemospan (MP4OX), Ringer's lactate
- Keywords
- Anesthesia, spinal, Blood substitutes, Oxygen therapeutics, Orthopedic surgery, Plasma expanders, Vasoconstriction, Hemospan
- Medical subject headings
- Hypotension, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hemospan (MP4OX)Drug
Also called MP4OX solution, 4.3 g/dL MalPEG-Hb, PEGylated Hb
200, 400, 600, 750, or 1000 mL of Hemospan (MP4OX)
Ringer's lactateDrug
Also called Lactated Ringers, Ringers solution, Hartmann's solution
200, 400, 600, 750, or 1000 mL of Ringer's lactate solution
| Study group | Role | What they receive |
|---|---|---|
| Hemospan (MP4OX) | Experimental | 4.3 g/dL MalPEG-Hb solution Receives: Drug: Hemospan (MP4OX) |
| Control | Active comparator | Ringer's lactate Receives: Drug: Ringer's lactate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Measured: 21 days
Secondary outcomes (9)
Changes from baseline in pulse oximetry
Measured: 4 days
Change in Arterial blood gas and blood lactate levels from baseline
Measured: 4 days
Duration of supplemental inspired oxygen [FIO2]
Measured: 4 days
Number and duration of intra-operative hypotensive episodes (SBP<90 mmHg or a DBP <50 mmHg)
Measured: 4 days
Incidence of pharmacologic intervention for hypotension
Measured: 4 days
Volume blood products administered
Measured: 4 days
Change from baseline in vital signs
Measured: 4 days
Changes in serum chemistry and hematology from baseline
Measured: 4 days
Volume of IV fluids given
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2007 (estimated)
- Study startApr 2003
- Primary completionJul 2006
- Study completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HypotensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sangart
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christina I. Olofsson, MD, PhD, Principal investigator, Karolinska University Hospital, Stockholm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00494949
- Sponsor's protocol ID
- 3002
- Status last verified
- Aug 2013
- First submitted
- 28 Jun 2007
- Last updated
- 19 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 15820947Winslow RM. Red cell substitutes. Semin Hematol. 2007 Jan;44(1):51-9. doi: 10.1053/j.seminhematol.2006.09.013.
PubMed 17198847Olofsson 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.
PubMed 17122578
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Safety (Phase Ib/II) Increasing Dose Study of MP4 (Hemospan) in Orthopedic Surgery Patients
- ClinicalTrials.gov ID
- NCT00494949
- Acronym / sponsor ID
- 3002
- Conditions
- Hypotension, Hypoxia
- Keywords
- Anesthesia, spinal, Blood substitutes, Oxygen therapeutics, Orthopedic surgery, Plasma expanders, Vasoconstriction, Hemospan
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- SangartIndustry (pharma, biotech, devices)
- Study start
- Apr 2003
- Primary completion
- Jul 2006 (actual)
- Study completion
- Aug 2006 (actual)
- First posted
- 2 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hemospan (MP4OX) | Experimental | Drug: Hemospan (MP4OX)4.3 g/dL MalPEG-Hb solution |
| Control | Active comparator | Drug: Ringer's lactateRinger's lactate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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, β-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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hemospan (MP4OX)Also: MP4OX solution, 4.3 g/dL MalPEG-Hb, PEGylated Hb200, 400, 600, 750, or 1000 mL of Hemospan (MP4OX) | Drug | Hemospan (MP4OX) |
| Ringer's lactateAlso: Lactated Ringers, Ringers solution, Hartmann's solution200, 400, 600, 750, or 1000 mL of Ringer's lactate solution | Drug | Control |
Primary outcome
Incidence of adverse events
Time frame: 21 days
9 secondary outcomes
Changes from baseline in pulse oximetry
Time frame: 4 days
Change in Arterial blood gas and blood lactate levels from baseline
Time frame: 4 days
Duration of supplemental inspired oxygen [FIO2]
Time frame: 4 days
Number and duration of intra-operative hypotensive episodes (SBP<90 mmHg or a DBP <50 mmHg)
Time frame: 4 days
Incidence of pharmacologic intervention for hypotension
Time frame: 4 days
Volume blood products administered
Time frame: 4 days
Change from baseline in vital signs
Time frame: 4 days
Changes in serum chemistry and hematology from baseline
Time frame: 4 days
Volume of IV fluids given
Time frame: 4 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2013.
- Background: PubMed 15820947Bjorkholm 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.
- Background: PubMed 17198847Winslow RM. Red cell substitutes. Semin Hematol. 2007 Jan;44(1):51-9. doi: 10.1053/j.seminhematol.2006.09.013.
- Results publication: PubMed 17122578Olofsson 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.
- Click here for more information about SangartLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christina I. Olofsson, MD, PhD principal investigator
Karolinska University Hospital, Stockholm
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Hemospan (MP4OX) and Ringer's lactate in people with Hypotension and Hypoxia, run by Sangart at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00494949, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2013.