- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT01648036
Heparin Anticoagulation to Improve Outcomes in Septic Shock: The HALO Pilot
9. července 2014 aktualizováno: Dr. Ryan Zarychanski, University of Manitoba
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.
Přehled studie
Postavení
Dokončeno
Podmínky
Intervence / Léčba
Typ studie
Intervenční
Zápis (Aktuální)
76
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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-
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Quebec, Kanada, G1J 1Z4
- Hôpital de L'Enfant-Jésus
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Manitoba
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Winnipeg, Manitoba, Kanada, R2H 2A6
- St. Boniface Hospital
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Winnipeg, Manitoba, Kanada, R3A 1R9
- Winnipeg Health Sciences Centre
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Nova Scotia
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Halifax, Nova Scotia, Kanada, B3H 3A7 and B3H 2Y9
- Capital Health - Queen Elizabeth II Health Sciences Centre
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Ontario
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Hamilton, Ontario, Kanada, L8L 2X2
- Hamilton General Hospital
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Hamilton, Ontario, Kanada, L8N 4A6
- St Joseph's Healthcare Hamilton
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Ottawa, Ontario, Kanada, K1H 8L6
- Ottawa Hospital General Campus
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Ottawa, Ontario, Kanada, K1Y 4E9
- Ottawa Hospital Civic Campus
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Toronto, Ontario, Kanada, M5B 1W8
- St Michael's Hospital
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- ≥ 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
Exclusion Criteria:
- 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.
- 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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Trojnásobný
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Unfractionated Heparin
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Dose: 18 IU/kg/hr, continuous intravenous infusion.
Duration: up to 7 days or until ICU discharge or death
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Aktivní komparátor: Dalteparin
Standard of care
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Dose 5000 IU, subcutaneous, daily
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Feasibility of enrollment - to enrol an average of 2 patients per site per month over the duration of the study
Časové okno: 1 year
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The primary measure of feasibility is the ability of participating sites to enroll an average of 2 patients per month.
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1 year
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Feasibility(1) - Consent rate - will be considered adequate if 60% of eligible patients are enrolled in the HALO pilot
Časové okno: 1 year
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1 year
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Safety - Rate of major and minor bleeding events
Časové okno: Duration of ICU admission, or up to day +9
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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.
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Duration of ICU admission, or up to day +9
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Activation of coagulation - Thrombin-antithrombin (TAT) complexes
Časové okno: Day 1, 2, 3, 5, 7, and 9 (or ICU discharge)
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Day 1, 2, 3, 5, 7, and 9 (or ICU discharge)
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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
Časové okno: Duration of study drug infusion or up to a maximum of 7 days
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Duration of study drug infusion or up to a maximum of 7 days
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Feasibility(3) - Time from randomization to initiation of study drug
Časové okno: the outcome will be assessed during the first 24 hours of enrollment
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The investigators will consider the time from randomization to study treatment initiation to be satisfactory if this interval is less than 4 hours.
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the outcome will be assessed during the first 24 hours of enrollment
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Activation of coagulation - Protein C concentration
Časové okno: Day 1, 2, 3, 5, 7, and 9 (or ICU discharge)
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Day 1, 2, 3, 5, 7, and 9 (or ICU discharge)
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Activation of Coagulation - Quantitative d-dimer
Časové okno: Days 1, 2, 3, 5, 7, and 9 (or ICU discharge)
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Days 1, 2, 3, 5, 7, and 9 (or ICU discharge)
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Markers of Inflammation (IL-6, IL-8, IL-10, and IL-17)
Časové okno: Days 1, 2, 3, 5, 7, and 9 (or ICU discharge)
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Days 1, 2, 3, 5, 7, and 9 (or ICU discharge)
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ICU Mortality (Tertiary, descriptive outcome only)
Časové okno: Will be assessed at the time of ICU discharge or death; expected average length of ICU admission is 5.7 days
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Will be assessed at the time of ICU discharge or death; expected average length of ICU admission is 5.7 days
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Hospital Mortality (Tertiary, descriptive outcome only)
Časové okno: Will be assessed at the time of hospital discharge or death; expected average length of hospital admission is 14 days
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Will be assessed at the time of hospital discharge or death; expected average length of hospital admission is 14 days
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Change in MODS score (Tertiary, descriptive outcome only)
Časové okno: Will be assessed daily during admission to the ICU; expected average length of ICU admission is 5.7 days
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Will be assessed daily during admission to the ICU; expected average length of ICU admission is 5.7 days
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Ryan Zarychanski, MD MSc, University of Manitoba
- Vrchní vyšetřovatel: Dean Fergusson, PhD MHA, Ottawa Hospital Research Institute
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. července 2012
Primární dokončení (Aktuální)
1. ledna 2014
Dokončení studie (Aktuální)
1. února 2014
Termíny zápisu do studia
První předloženo
14. července 2012
První předloženo, které splnilo kritéria kontroly kvality
19. července 2012
První zveřejněno (Odhad)
24. července 2012
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
10. července 2014
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
9. července 2014
Naposledy ověřeno
1. července 2014
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- HCA2011/001
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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