SepsisPhase 3NCT00100308
Unfractioned Heparin for Treatment of Sepsis
A Phase 3 study testing Unfractioned heparin and saline in people with Sepsis and Bacterial Infections, run by Universidad de Antioquia at 1 site in Colombia.
Trial summary
The purpose of this study is to determine whether low dose continuous infusion of unfractioned heparin (500 units/hour), in addition to the standard treatment, is efficacious as complementary therapy for sepsis patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Bacterial Infections
- What is being tested?
- Unfractioned heparin and saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 319 participants
- Where
- 1 siteColombia
- Study dates
- Jul 2005to Jul 2007
- Phase
- Phase 3
- 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
- Patients must have an infection defined by clinical and/or microbiological criteria in accordance with modified CDC definitions for nosocomial infections
- Patients must present with one or more of the GENERAL VARIABLES, AND one or more of the INFLAMMATORY VARIABLES within 24 hours before admission to the study
- GENERAL VARIABLES:
- Temperature (oral or axillary) > 38ºC or < 36ºC,
- Heart rate > 90 beats/min,
- Respiratory rate > 20 breaths/min,
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- Altered mental status determined by Glasgow Coma Scale < 15,
- Systolic blood pressure < 90 mm Hg or a decrease > 40 mm Hg
- INFLAMMATORY VARIABLES:
- WBC > 12,000 μL-1 or < 4,000 μL-1 or with > 10% immature forms,
- Plasma C-reactive protein > 5 mg/dL.
- These variables should not be attributable to an underlying disease other than infection or due to the effects of concomitant therapy.
Who cannot join
- Pregnant or breastfeeding.
- Platelet count < 60,000/mm3.
- Increased risk for bleeding: * Any patient who has undergone major surgery, defined as surgery that required general or spinal anesthesia, performed within the 12-hour period immediately preceding admission to the hospital; any postoperative patient who demonstrates evidence of active bleeding; or any patient with planned or anticipated major surgery during the first 12 hours after admission to the hospital. * History of: severe head trauma that required hospitalization, intracranial surgery, or stroke within 3 months of study entry; or any history of intracerebral arteriovenous malformation, cerebral aneurysm, or central nervous system mass lesion. * History of congenital bleeding diatheses, such as hemophilia. * Gastrointestinal bleeding within 6 weeks of study entry that required medical intervention unless definitive surgery has been performed. * Trauma patients at increased risk of bleeding, for example: flail chest; significant contusion to lung, liver, or spleen; retroperitoneal bleed; pelvic fracture; or compartment syndrome.
- Patients with a known hypercoagulable condition including activated Protein C resistance; a hereditary deficiency of Protein C, Protein S, or antithrombin; presence of anticardiolipin antibody, antiphospholipid syndrome, lupus anticoagulant or homocysteinemia; or patients with a recently documented (within 3 months of study entry) or highly suspected deep venous thrombosis or pulmonary embolism.
- Patients taking or requiring the following medications: * Therapeutic heparin, defined as UFH dosed to treat an active thrombotic or embolic event within the 12 hours prior to study entry or LMWH used at any dose higher or more frequent than the recommended dose on the product label for prophylaxis within the 12 hours prior to study entry. * Warfarin, if used within 7 days of study entry. * Thrombolytic treatment within 3 days of study entry (for example, streptokinase, rtPA, and urokinase). * Glycoprotein IIb/IIIa antagonists within 7 days of study entry.
- Patients with known esophageal varices, chronic jaundice, cirrhosis, or chronic ascites.
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- Patients not expected to survive 28 days given their preexisting, uncorrectable medical condition. This criterion includes patients with, or suspected to have, poorly controlled neoplasms or other end-stage processes, such as end-stage cardiac disease, prior cardiac arrest, end-stage lung disease, or end-stage liver disease.
- Patients with chronic renal failure on either hemodialysis or peritoneal dialysis.
- HIV positive patients with most recent CD4 count < 200/mm3.
- Patients who have undergone bone marrow, liver, lung, kidney or pancreas transplantation.
- Inability or unwillingness of patients or legal representative to give written informed consent.
Trial locations and contacts
1 site in 1 country.
Colombia1 site
Hospital Universitario San Vicente de Paul
Medellín, Antioquia
About this study
Official title: Unfractioned Heparin for Treatment of Sepsis: A Randomized Clinical Trial (The HETRASE Study)
The purpose of this study is to determine whether low dose continuous infusion of unfractioned heparin (500 units/hour), in addition to the standard treatment, is efficacious as complementary therapy for sepsis patients.
Read the detailed description
Sepsis is considered a leading cause of death worldwide with approximately 18 million cases annually and a mortality rate of almost 30%. The search for efficacious therapeutic approaches has largely failed and only a few of the recent interventions, such as activated protein C and low dose steroids, have shown some success in improving survival. However, these interventions were tested only in patients with severe sepsis and/or septic shock and although these groups exhibit the highest mortality, they represent less than 50% of the total affected population. Furthermore, these interventions necessitate special devices, tests and/or drugs that might be unavailable or simply unaffordable in resource-limited settings.
Animal and human models have suggested that heparin, in addition to successfully inhibiting the coagulation cascade, may also modulate the wide array of responses to infection. Furthermore, the three clinical trials for recombinant anticoagulants allowed the use of prophylactic treatment for venous thrombosis with a dose of unfractioned heparin (UFH) of up to 10,000 or 15,000 units subcutaneously per day. When those who did receive heparin were compared to those who did not in the placebo arms of the clinical trials, all three studies showed a higher mortality in the subgroups that did not receive heparin. Although this is not a randomized comparison, a constant result in three different study populations with variable entry criteria, along with the natural heterogeneity of the illness, strongly fosters the hypothesis that heparin might reduce, beyond its known anticoagulant and antithrombotic properties, the overall mortality for sepsis.
In this project, we propose a phase II/III, randomized, double-masked, placebo-controlled, single-center clinical trial with a total sample size of 310 patients, for testing low dose continuous infusions of UFH (500 units/hour) for 7 days, as complementary treatment for septic patients. Our primary aims are to estimate the effects of UFH on length of stay and change from baseline Multiple Organic Dysfunction (MOD) score. Secondary objectives are to estimate the effects of UFH on 28-day all-cause mortality, and to estimate the possible effect-modification on 28-day all-cause mortality, in subgroups defined by site of infection and baseline values of APACHE II score, MOD score and D-dimer.
- Conditions
- Sepsis, Bacterial Infections
- Being tested
- Unfractioned heparin, saline
- Keywords
- sepsis, Randomized clinical trial, Heparin, Therapy
- Medical subject headings
- Sepsis, Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Unfractioned heparinDrug
Low-dose continuous-infusion, 500 units/hour per seven days
salineDrug
Saline placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Standard treatment plus unfractioned heparin low-dose continuous infusion Receives: Drug: Unfractioned heparin |
| 2 | Placebo comparator | Standard treatment plus placebo Receives: Drug: saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline Multiple Organ Dysfunction (MOD) score
Measured: 15 days
Length of stay
Measured: During hospitalization
Secondary outcomes (1)
28-day all-cause mortality
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2004 (estimated)
- Study startJul 2005
- Primary completionJul 2007
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 319 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidad de Antioquia
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología (COLCIENCIAS)
- Investigators
- Fabián A Jaimes, MD, MSc, PhD, Principal investigator, Universidad de Antioquia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00100308
- Sponsor's protocol ID
- COLCIENCIAS -11150416347
- Status last verified
- Jan 2008
- First submitted
- 28 Dec 2004
- Last updated
- 15 Jan 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unfractioned Heparin for Treatment of Sepsis: A Randomized Clinical Trial (The HETRASE Study)
- ClinicalTrials.gov ID
- NCT00100308
- Acronym / sponsor ID
- COLCIENCIAS -11150416347
- Conditions
- Sepsis, Bacterial Infections
- Keywords
- sepsis, Randomized clinical trial, Heparin, Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 319 participants (actual)
- Lead sponsor
- Universidad de AntioquiaUniversity, hospital or other
- Collaborators
- Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología (COLCIENCIAS)
- Study start
- Jul 2005
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 29 Dec 2004 (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 determine whether low dose continuous infusion of unfractioned heparin (500 units/hour), in addition to the standard treatment, is efficacious as complementary therapy for sepsis patients.
Detailed description
Sepsis is considered a leading cause of death worldwide with approximately 18 million cases annually and a mortality rate of almost 30%. The search for efficacious therapeutic approaches has largely failed and only a few of the recent interventions, such as activated protein C and low dose steroids, have shown some success in improving survival. However, these interventions were tested only in patients with severe sepsis and/or septic shock and although these groups exhibit the highest mortality, they represent less than 50% of the total affected population. Furthermore, these interventions necessitate special devices, tests and/or drugs that might be unavailable or simply unaffordable in resource-limited settings.
Animal and human models have suggested that heparin, in addition to successfully inhibiting the coagulation cascade, may also modulate the wide array of responses to infection. Furthermore, the three clinical trials for recombinant anticoagulants allowed the use of prophylactic treatment for venous thrombosis with a dose of unfractioned heparin (UFH) of up to 10,000 or 15,000 units subcutaneously per day. When those who did receive heparin were compared to those who did not in the placebo arms of the clinical trials, all three studies showed a higher mortality in the subgroups that did not receive heparin. Although this is not a randomized comparison, a constant result in three different study populations with variable entry criteria, along with the natural heterogeneity of the illness, strongly fosters the hypothesis that heparin might reduce, beyond its known anticoagulant and antithrombotic properties, the overall mortality for sepsis.
In this project, we propose a phase II/III, randomized, double-masked, placebo-controlled, single-center clinical trial with a total sample size of 310 patients, for testing low dose continuous infusions of UFH (500 units/hour) for 7 days, as complementary treatment for septic patients. Our primary aims are to estimate the effects of UFH on length of stay and change from baseline Multiple Organic Dysfunction (MOD) score. Secondary objectives are to estimate the effects of UFH on 28-day all-cause mortality, and to estimate the possible effect-modification on 28-day all-cause mortality, in subgroups defined by site of infection and baseline values of APACHE II score, MOD score and D-dimer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Unfractioned heparinStandard treatment plus unfractioned heparin low-dose continuous infusion |
| 2 | Placebo comparator | Drug: salineStandard treatment plus placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must have an infection defined by clinical and/or microbiological criteria in accordance with modified CDC definitions for nosocomial infections
- Patients must present with one or more of the GENERAL VARIABLES, AND one or more of the INFLAMMATORY VARIABLES within 24 hours before admission to the study
- Temperature (oral or axillary) > 38ºC or < 36ºC,
- Heart rate > 90 beats/min,
- Respiratory rate > 20 breaths/min,
Key exclusion criteria (11 listed)
- Pregnant or breastfeeding.
- Platelet count < 60,000/mm3.
- Increased risk for bleeding: * Any patient who has undergone major surgery, defined as surgery that required general or spinal anesthesia, performed within the 12-hour period immediately preceding admission to the hospital; any postoperative patient who demonstrates evidence of active bleeding; or any patient with planned or anticipated major surgery during the first 12 hours after admission to the hospital. * History of: severe head trauma that required hospitalization, intracranial surgery, or stroke within 3 months of study entry; or any history of intracerebral arteriovenous malformation, cerebral aneurysm, or central nervous system mass lesion. * History of congenital bleeding diatheses, such as hemophilia. * Gastrointestinal bleeding within 6 weeks of study entry that required medical intervention unless definitive surgery has been performed. * Trauma patients at increased risk of bleeding, for example: flail chest; significant contusion to lung, liver, or spleen; retroperitoneal bleed; pelvic fracture; or compartment syndrome.
- Patients with a known hypercoagulable condition including activated Protein C resistance; a hereditary deficiency of Protein C, Protein S, or antithrombin; presence of anticardiolipin antibody, antiphospholipid syndrome, lupus anticoagulant or homocysteinemia; or patients with a recently documented (within 3 months of study entry) or highly suspected deep venous thrombosis or pulmonary embolism.
- Patients taking or requiring the following medications: * Therapeutic heparin, defined as UFH dosed to treat an active thrombotic or embolic event within the 12 hours prior to study entry or LMWH used at any dose higher or more frequent than the recommended dose on the product label for prophylaxis within the 12 hours prior to study entry. * Warfarin, if used within 7 days of study entry. * Thrombolytic treatment within 3 days of study entry (for example, streptokinase, rtPA, and urokinase). * Glycoprotein IIb/IIIa antagonists within 7 days of study entry.
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 |
|---|---|---|
| Unfractioned heparinLow-dose continuous-infusion, 500 units/hour per seven days | Drug | 1 |
| salineSaline placebo | Drug | 2 |
Primary outcome
Change from baseline Multiple Organ Dysfunction (MOD) score
Time frame: 15 days
Length of stay
Time frame: During hospitalization
1 secondary outcome
28-day all-cause mortality
Time frame: 28 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 15 Jan 2008.
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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.
Fabián A Jaimes, MD, MSc, PhD principal investigator
Universidad de Antioquia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Unfractioned heparin and saline in people with Sepsis and Bacterial Infections, run by Universidad de Antioquia at 1 site in Colombia.
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 12 inclusion and 11 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 15 Jan 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Colombia. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Change from baseline Multiple Organ Dysfunction (MOD) score (time frame: 15 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jan 2008; AzTrials last refreshed its copy on 7 Nov 2026.