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Septic ShockPhase 2NCT01648036

Heparin Anticoagulation to Improve Outcomes in Septic Shock: The HALO Pilot

A Phase 2 study testing Unfractionated heparin and Dalteparin in people with Septic Shock, run by University of Manitoba at 9 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Life-threatening infections account for 10% of all intensive care unit admissions and constitute the second more frequent cause of death in the ICU after heart diseases. The most common cause of death in patients admitted with life-threatening infections is multi-organ failure that is mediated by severe inflammation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Septic Shock
What is being tested?
Unfractionated heparin and Dalteparin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
76 participants
Where
9 sitesCanada
Study dates
Jul 2012to Feb 2014
Phase
Phase 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

  • ≥ 18 years of age
  • Refractory hypotension documented within 36 hours prior to enrolment that requires institution and ongoing use of vasopressor agents (phenylephrine, norepinephrine, vasopressin, epinephrine, or dopamine > 5 mcg/kg/min) at the time of enrolment. Refractory hypotension is defined as a systolic blood pressure < 90 mmHG or a systolic blood pressure more than 30 mmHg below baseline, or a mean arterial pressure less than 65 mmHG and receipt of greater than or equal to 2 litres of intravenous fluid for the treatment of hypotension.
  • At least 1 other new organ dysfunction defined by the following:
  • Creatinine ≥ 150 µmol/L, or ≥ 1.5x the upper limit of normal or the known baseline creatinine, or < 0.5 ml/kg or urine output for 2 hours(Patients on chronic hemodialysis or peritoneal dialysis must meet one of the following criteria)
  • Need for invasive mechanical ventilation or a P/F ratio < 250
  • Platelets < 100 x109/L, or a drop of 50 x109/L in the 3 days prior to enrollment
  • Arterial pH < 7.30 or base deficit > 5 mmol/L in association with a lactate >/= to 3.0 mmol/L

Who cannot join

  • Consent declined
  • Clinically apparent other forms of shock including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponnade, tension pneumothorax), hemorrhagic, neurogenic, or anaphylactic
  • Received vasopressor therapy for greater than 36 hours prior to enrollment
  • Have a significant risk of bleeding as evidenced by one of the following:
  • Clinical: Surgery requiring general or spinal anesthesia within 24 hours prior to enrollment, or the potential need for such surgery in the next 24 hours; evidence of active bleeding; a history of severe head trauma requiring hospitalization; intracranial surgery, or stroke within 3 months before the study or any history of intracerebral arteriovenous malformation, cerebral aneurysm, or mass lesions of the central nervous system; a history of congenital bleeding diatheses; gastrointestinal bleeding within 6 weeks before the study unless corrective surgery had been performed; trauma considered to increase the risk of bleeding; presence of an epidural catheter
  • Laboratory: Platelet count < 30 x109/L, INR > 2.0, or baseline aPTT > 50 sec prior to enrollment.
Show all 14Show fewer
  • Have an indication for therapeutic anticoagulation (e.g. ACS, acute VTE, mechanical valve, etc)
  • Intent of the most responsible physician to prescribe rhAPC
  • Have had a known or suspected adverse reaction to UFH including HIT
  • Are currently enrolled in related trial
  • Known or suspected cirrhosis, or chronic ascites
  • Use of any of the following medications or treatment regimens: unfractionated heparin to treat an active thrombotic event within 12 hours before the infusion enrollment; low-molecular-weight heparin at a higher dose than recommended for prophylactic use (as specified in the package insert) within 12 hours before the infusion; warfarin (if used within 7 days before study entry AND if the INR time exceeded the upper limit of the normal range for the institution); thrombolytic therapy within 3 days before the study, glycoprotein IIb/IIIa antagonists within 7 days before study entry; protein C or rhAPC within 24 hours before enrollment.
  • Terminal illness with a life expectancy of less than 3 months
  • Are pregnant

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Canada9 sites

  • Capital Health - Queen Elizabeth II Health Sciences Centre

    Halifax, Nova Scotia, B3H 3A7 and B3H 2Y9

  • Hamilton General Hospital

    Hamilton, Ontario, L8L 2X2

  • St Joseph's Healthcare Hamilton

    Hamilton, Ontario, L8N 4A6

  • Ottawa Hospital General Campus

    Ottawa, Ontario, K1H 8L6

  • Ottawa Hospital Civic Campus

    Ottawa, Ontario, K1Y 4E9

  • Hopital de l'Enfant-Jesus

    Québec, Quebec, G1J 1Z4

  • St Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • St. Boniface Hospital

    Winnipeg, Manitoba, R2H 2A6

  • Winnipeg Health Sciences Centre

    Winnipeg, Manitoba, R3A 1R9

Other trials in Canada

About this study

Life-threatening infections account for 10% of all intensive care unit admissions and constitute the second more frequent cause of death in the ICU after heart diseases. The most common cause of death in patients admitted with life-threatening infections is multi-organ failure that is mediated by severe inflammation. Given the relationship between inflammation and blood clotting, blood-thinners (also called anticoagulants) have been used to decrease inflammation and the formation of small clots. Several lines of evidence suggest that heparin, a proven and inexpensive blood-thinner, may reduce improve survival in patients diagnosed with life-threatening infection. The primary objective of this study is to demonstrate the feasibility of enrolling patients in a large randomized controlled trial investigating heparin in patients with severe infections. In this study, patients with life-threatening infections will have an equal chance of receiving an intravenous infusion of heparin, or a low dose of a similar drug to prevent of blood clots while patients are immobile. The primary purpose of the study is to demonstrate that an average of 2 patients per site, per month, can be enrolled. Other measures of feasibility include the consent rate, the number of protocol violations that occur during the trial, and the number of dose reductions needed due to excessive anticoagulation. To study the biologic effects of heparin in patients with severe infection, specific laboratory markers will be measured and analyzed. If the feasibility of the trial is confirmed, a large randomized trial designed to tell if heparin can safely improve survival will be conducted. Given its low cost and availability, if heparin is shown to improve survival in patients with severe infection, adoption of this therapy on a global scale is anticipated.

Conditions
Septic Shock
Being tested
Unfractionated heparin, Dalteparin
Medical subject headings
Shock, Septic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Unfractionated heparinDrug

    Dose: 18 IU/kg/hr, continuous intravenous infusion. Duration: up to 7 days or until ICU discharge or death

  • DalteparinDrug

    Also called Fragmin

    Dose 5000 IU, subcutaneous, daily

Study groups in NCT01648036
Study groupRoleWhat they receive
Unfractionated HeparinExperimentalNot described
Receives: Drug: Unfractionated heparin
DalteparinActive comparatorStandard of care
Receives: Drug: Dalteparin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility of enrollment - to enrol an average of 2 patients per site per month over the duration of the study

    The primary measure of feasibility is the ability of participating sites to enroll an average of 2 patients per month.

    Measured: 1 year

Secondary outcomes (11)

  1. Feasibility(1) - Consent rate - will be considered adequate if 60% of eligible patients are enrolled in the HALO pilot

    Measured: 1 year

  2. Safety - Rate of major and minor bleeding events

    a.) Rates of major and minor bleeding will be adjudicated and will be considered in the context of monitored aPTTs: 1) in the context of aPTTs ≤95 seconds, the rate of major bleeding will be deemed acceptable if major bleeding occurs in ≤10% of patients; and 2) if >20% of patients require an initial (6 hour aPTT) dose reduction of the study drug due to an aPTT >95 seconds, this dose will be deemed infeasible as an initiation dose.

    Measured: Duration of ICU admission, or up to day +9

  3. Activation of coagulation - Thrombin-antithrombin (TAT) complexes

    Measured: Day 1, 2, 3, 5, 7, and 9 (or ICU discharge)

  4. Feasibility(2): Protocol Deviations - The investigators believe that an acceptable rate of protocol violations resulting in a non-scheduled dose reduction or interruption of the study drug to be less than 10% of all study drug dose adjustments

    Measured: Duration of study drug infusion or up to a maximum of 7 days

  5. Feasibility(3) - Time from randomization to initiation of study drug

    The investigators will consider the time from randomization to study treatment initiation to be satisfactory if this interval is less than 4 hours.

    Measured: the outcome will be assessed during the first 24 hours of enrollment

  6. Activation of coagulation - Protein C concentration

    Measured: Day 1, 2, 3, 5, 7, and 9 (or ICU discharge)

  7. Activation of Coagulation - Quantitative d-dimer

    Measured: Days 1, 2, 3, 5, 7, and 9 (or ICU discharge)

  8. Markers of Inflammation (IL-6, IL-8, IL-10, and IL-17)

    Measured: Days 1, 2, 3, 5, 7, and 9 (or ICU discharge)

  9. ICU Mortality (Tertiary, descriptive outcome only)

    Measured: Will be assessed at the time of ICU discharge or death; expected average length of ICU admission is 5.7 days

  10. Hospital Mortality (Tertiary, descriptive outcome only)

    Measured: Will be assessed at the time of hospital discharge or death; expected average length of hospital admission is 14 days

  11. Change in MODS score (Tertiary, descriptive outcome only)

    Measured: Will be assessed daily during admission to the ICU; expected average length of ICU admission is 5.7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jul 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionJan 2014
  4. Study completionFeb 2014

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
76 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01648036
Sponsor's protocol ID
HCA2011/001
Status last verified
Jul 2014
First submitted
14 Jul 2012
Last updated
10 Jul 2014
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Unfractionated heparin and Dalteparin in people with Septic Shock, run by University of Manitoba at 9 sites in Canada.

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 7 inclusion and 14 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 10 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Canada. 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 phase mean?

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?

Feasibility of enrollment - to enrol an average of 2 patients per site per month over the duration of the study (time frame: 1 year). 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 NCT01648036.

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 10 Jul 2014.

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