Significant Bleeding RiskPhase 3NCT02740335
Study of Octaplex, a Four-factor Prothrombin Complex Concentrate (4F-PCC) and Beriplex® P/N (Kcentra) for the Reversal of Vitamin K Antagonist (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk.
A Phase 3 study testing Octaplex and Beriplex P/N (Kcentra) in people with Significant Bleeding Risk, run by Octapharma at 86 sites in 11 countries.
Trial summary
To demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under Vitamin K Antagonist (VKA) therapy with the need for urgent surgery with significant bleeding risk is clinically non-inferior to that Beriplex® P/N (Kcentra). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Significant Bleeding Risk
- What is being tested?
- Octaplex and Beriplex P/N (Kcentra)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 208 participants
- Where
- 86 sitesin 11 countries
- Study dates
- 8 Jun 2017to 23 Feb 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Male or female patients at least 18 years of age.
- Patients currently on oral anticoagulation treatment with VKA of coumadin or warfarin type.
- Patients being admitted to the hospital or currently hospitalized where:
- an urgent surgery carrying significant bleeding risk (≥50 mL expected blood loss) is required as part of routine clinical care;
- the use of oral or parenteral vitamin K alone to reverse anticoagulation is deemed too slow or inappropriate for reversal;
- Patients with an international normalized ratio (INR) of 2.0 or above at the time of decision to reverse the anticoagulation status.
- Patients who have given written informed consent and who are able and willing to comply with the procedures described in the study protocol.
Who cannot join
- Patients with a life expectancy of less than 48 hours per physician's judgment (e.g. patients with a Glasgow Coma Scale equal to 3 or a Head Abbreviated Injury Score of 6, patients requiring continuous inotropic or pressor support, and patients whose status is post cardiac arrest).
- Patients for whom the planned surgery or procedure is commonly associated with a very low bleeding risk (e.g. catheter placement, gastroscopy).
- Patients with a history of thromboembolic events (TEEs), myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebrovascular accident, transient ischemic attack, severe peripheral vascular disease, or disseminated intravascular coagulation within 3 months of enrollment.
- Patients with a known congenital bleeding disorder.
- Patients with a known antiphospholipid antibody syndrome.
- Patients with present or past specific factor inhibitor activity.
Show all 14Show fewer
- Patients with thrombocytopenia of <80,000/μL or history of heparin-induced thrombocytopenia.
- Patients who have received heparin of any type or any non-VKA anticoagulant within 24 hours prior to enrollment into the study or with potential need to receive these medications before completion of hemostasis evaluation at the end of surgery.
- Patients who have received prothrombin complex concentrates (PCCs), fresh frozen plasma or vitamin K within 72 hours prior to enrollment into the study.
- Patients with a known history of hypersensitivity to plasma-derived products.
- Patients with acute major bleeding or polytrauma.
- Pregnant or nursing women.
- Patients participating in another interventional clinical study currently or during the past 30 days prior to enrollment into this study.
- Patients previously enrolled in this study.
Trial locations and contacts
86 sites in 11 countries.
86 sites in 11 countries
United States22 sites
Octapharma Research Site
Aurora, Colorado, 80045
Octapharma Research Site (0115)
Austin, Texas, 78701
Octapharma Research Site (0127)
Austin, Texas, 78701
Octapharma Research Site
Boston, Massachusetts, 02114
Octapharma Research Site
Cleveland, Ohio, 44109
Octapharma Research Site
Columbus, Ohio, 43210
Octapharma Research Site
Dallas, Texas, 75390
Octapharma Research Site
Dayton, Ohio, 45409
Octapharma Research Site
Durham, North Carolina, 27710
Octapharma Research Site
Fairborn, Ohio, 45324
Octapharma Research Site
Iowa City, Iowa, 52242
Octapharma Research Site
Miami, Florida, 33136
Octapharma Research Site
New Haven, Connecticut, 06510
Octapharma Research Site
Pittsburgh, Pennsylvania, 15213
Octapharma Study Site
Pittsburgh, Pennsylvania, 15213
Octapharma Research Site
Pittsburgh, Pennsylvania, 15219
Octapharma Research Site
Pittsburgh, Pennsylvania, 15232
Octapharma Research Site
Pittsburgh, Pennsylvania, 15237
Octapharma Research Site
Puyallup, Washington, 98374
Octapharma Research Site
Rochester, New York, 14642
Octapharma Research Site
Round Rock, Texas, 78665
Octapharma Research Site
Tampa, Florida, 33606
Ukraine17 sites
Octapharma Research Site
Cherkasy, 18009
Octapharma Research Site
Chernivtsi, 58001
Octapharma Research Location
Dnipro, 49005
Octapharma Research Site
Dnipro, 49005
Octapharma Research Site
Dnipro, 49102
Octapharma Research Site
Ivano-Frankivsk, 76018
Octapharma Research Site
Kharkiv, 61037
Octapharma Research Site
Kharkiv, 61103
Octapharma Research Site
Kropyvnytskyi, 25006
Octapharma Research Site
Kyiv, 01133
Octapharma Research Site
Lutsk, 43006
Octapharma Research Site
Lviv, 79010
Octapharma Research Site
Lviv, 79034
Octapharma Research Site
Odesa, 65006
Octapharma Research Site
Vinnytsia, 21018
Octapharma Research Site
Zaporizhzhya, 69000
Octapharma Research Site
Zhytomyr, 12430
Russia14 sites
Octapharma Research Site
Moscow, Russian Federation, 105203
Octapharma Research Site
Moscow, 111539
Octapharma Research Site
Moscow, 115446
Octapharma Research Site
Moscow, 124489
Octapharma Research Site
Novosibirsk, Russian Federation, 630055
Octapharma Research Site
Omsk, Russian Federation, 644111
Octapharma Research Site
Saint Petersburg, Russian Federation, 192242
Octapharma Research Site
Saint Petersburg, Russian Federation, 194354
Octapharma Research Site
Saint Petersburg, Russian Federation, 197022
Octapharma Research Site
Saint Petersburg, 194354
Regional Clinical Hospital
Saratov, Russian Federation, 410053
Octapharma Research Site
Smolensk, 214019
Octapharma Research Site
Tver', Russian Federation, 170036
Octapharma Research Site
Yekaterinburg, Russian Federation, 620026
Georgia8 sites
Octapharma Research Site
Batumi, 6010
Octapharma Research Site
Kutaisi, 4600
Octapharma Research Site - Tbilisi
Tbilisi, 00114
Octapharma Research Location - Tbilisi
Tbilisi, 00167
Octapharma Research Site
Tbilisi, 0141
Octapharma Research Location
Tbilisi, 0159
Octapharma Research Site
Tbilisi, 0159
Octapharma Research Site
Zugdidi, 2100
Romania6 sites
Octapharma Research Site
Bucharest, 010825
Octapharma Research Site
Bucharest, 020475
Octapharma Research Site
Cluj-Napoca, 400006
Octapharma Research Site
Craiova, 200624
Octapharma Research Site
Oradea, 410167
Octapharma Research Site
Timișoara, 3000723
Bulgaria5 sites
Octapharma Research Site
Plovdiv, 4002
Octapharma Research Site
Rousse, 7002
Octapharma Research Site
Sofia, 1000
Octapharma Study Site
Sofia, 1000
Octapharma Research Site
Varna, 9010
Belarus4 sites
Octapharma Research Site
Lesnoy, 223040
Octapharma Research Site
Minsk, 220024
Octapharma Research Site
Minsk, 220032
Octapharma Research Site
Minsk, 220040
Germany4 sites
Octapharma Research Site
Berlin, 12559
Octapharma Research Site
Dresden, 01307
Octapharma Research Site
Frankfurt am Main, 60590
Octapharma Research Site
Heidelberg, 69120
Spain3 sites
Octapharma Research Site
Barcelona, 08907
Octapharma Research Site
Palma de Mallorca, 07120
Octapharma Research Site
Valencia, 46026
Poland2 sites
Octapharma Research Site
Bochnia, 32-700
Octapharma Research Site
Lodz, 95-513
About this study
Official title: A Phase III, Randomized, Double-blind, Multicenter Study to Assess the Efficacy and Safety of OCTAPLEX, a Four-factor Prothrombin Complex Concentrate (4F-PCC), Compared to the 4F-PCC Beriplex® P/N (Kcentra), for the Reversal of Vitamin K Antagonist (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk.
To demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under Vitamin K Antagonist (VKA) therapy with the need for urgent surgery with significant bleeding risk is clinically non-inferior to that Beriplex® P/N (Kcentra).
Read the detailed description
The primary objective of the study is to demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under Vitami n K Antagonist (VKA)therapy with the need for urgent surgery with significant bleeding risk is clinically non-inferior to that Beriplex® P/N (Kcentra).
The secondary objective of the study is to investigate the safety and tolerability of OCTAPLEX compared to Beriplex® P/N (Kcentra) in patients under Vitamin K Antagonist (VKA) therapy with the need for urgent surgery with significant bleeding risk.
- Conditions
- Significant Bleeding Risk
- Being tested
- Octaplex, Beriplex P/N (Kcentra)
- Keywords
- anticoagulant reversal, urgent surgery, invasive procedures, vitamin K, prothrombin complex concentrate, four-factor prothrombin complex concentrate (4F-PCC)
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OctaplexDrug
Also called 4F PCC, 4 Factor PCC, 4 Factor Prothrombin Concentrate Complex
OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
Beriplex P/N (Kcentra)Drug
Also called Kcentra
Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
| Study group | Role | What they receive |
|---|---|---|
| Octaplex | Experimental | Participants to receive1 Octaplex infusion intravenously Receives: Drug: Octaplex |
| Beriplex P/N (Kcentra) | Active comparator | Participants to receive1 Kcentra infusions intravenously Receives: Drug: Beriplex P/N (Kcentra) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemostatic Efficacy Rating by IEAB
Hemostatic Efficacy rated by the Independent Endpoint Adjudication Committee based on a 1 to 4 point hemostatic efficacy scale, taking into account blood loss and transfusion requirements in the context of the surgery. Hemostatic efficacy was assessed based on objective criteria in the categories 'excellent', 'good', 'moderate', or 'none'. Ratings of 'excellent' and 'good' were considered as 'effective' hemostasis, while ratings of 'moderate' and 'none' were considered as 'ineffective' hemostasis.
Measured: At the end of the surgery
Dichotomous Hemostasis Success
To demostrate clinical non-inferiority of treatment with Octaplex to treatment with Beriplex P/N (Kcentra) with respect to hemostatic success. Effective hemostatis includes Excellent and Good ratings, while Ineffective hemostasis includes Moderate, None and missing ratings from Global hemostatic efficacy observed by IEAB
Measured: At the end of surgery
Secondary outcomes (6)
Measuring of International Normalized Ratio (INR) to ≤ 1.5
Number of patients with an international normalized ratio (INR) value of less or equal to 1.5 at 30 min (± 15 min) after the end of infusion.
Measured: 30 minutes after the end of infusion
Coagulation Factor II Levels
Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor II
The Hodges-Lehmann Estimator is a method of robust estimation. This estimator is used to give an estimate of the difference between the values in two sets of data. If the two sets of data contain m and n data points respectively, m × n pairs of points (one from each set) can be formed and each pair gives a difference of values. The Hodges-Lehmann estimator for the difference is defined as the median of the m × n differences.
Measured: 30 minutes after the end of infusion
Coagulation Factor VII Levels
Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor VII
The Hodges-Lehmann Estimator is a method of robust estimation. This estimator is used to give an estimate of the difference between the values in two sets of data. If the two sets of data contain m and n data points respectively, m × n pairs of points (one from each set) can be formed and each pair gives a difference of values. The Hodges-Lehmann estimator for the difference is defined as the median of the m × n differences.
Measured: 30 minutes after the end of infusion
Coagulation Factor IX Levels
Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor II Factor IX
The Hodges-Lehmann Estimator is a method of robust estimation. This estimator is used to give an estimate of the difference between the values in two sets of data. If the two sets of data contain m and n data points respectively, m × n pairs of points (one from each set) can be formed and each pair gives a difference of values. The Hodges-Lehmann estimator for the difference is defined as the median of the m × n differences.
Measured: 30 minutes after the end of infusion
Coagulation Factor X Levels
Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor X
The Hodges-Lehmann Estimator is a method of robust estimation. This estimator is used to give an estimate of the difference between the values in two sets of data. If the two sets of data contain m and n data points respectively, m × n pairs of points (one from each set) can be formed and each pair gives a difference of values. The Hodges-Lehmann estimator for the difference is defined as the median of the m × n differences.
Measured: 30 minutes after the end of infusion
Number of Patients Requiring Red Blood Cells (RBC)
Number of patients receiving red blood cells (RBC) during the surgery
Measured: At the end of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2016 (estimated)
- Study start8 Jun 2017
- Primary completion23 Feb 2022
- Study completion23 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Significant Bleeding RiskStudies 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
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Lead sponsor
- Octapharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wolfgang Frenzel, Study director, International Medical Monitor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02740335
- Sponsor's protocol ID
- LEX-209
- Status last verified
- Mar 2023
- First submitted
- 5 Apr 2016
- Last updated
- 8 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006 Jul;105(1):198-208. doi: 10.1097/00000542-200607000-00030. No abstract available.
PubMed 16810012Campbell P, Roberts G, Eaton V. Managing warfarin therapy in the community. Aust Prescriber 2001; 24:86-89.
Cushman M, et al. Clinical Practice Guide on Antithrombotic Drug Dosing and Management of Antithrombotic Drug-Associated Bleeding Complications in Adults, American Society of Hematology, 2014.
Gohlke-Barwolf C. [Anticoagulation in surgery, after hemorrhagic complications and in pregnancy]. Z Kardiol. 1998;87 Suppl 4:56-62. German.
PubMed 9857468Goldstein JN, Refaai MA, Milling TJ Jr, Lewis B, Goldberg-Alberts R, Hug BA, Sarode R. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015 May 23;385(9982):2077-87. doi: 10.1016/S0140-6736(14)61685-8. Epub 2015 Feb 27.
PubMed 25728933Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of type I error probability spending functions. Stat Med. 1990 Dec;9(12):1439-45. doi: 10.1002/sim.4780091207.
PubMed 2281231Keeling D, Baglin T, Tait C, Watson H, Perry D, Baglin C, Kitchen S, Makris M; British Committee for Standards in Haematology. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol. 2011 Aug;154(3):311-24. doi: 10.1111/j.1365-2141.2011.08753.x. Epub 2011 Jun 14. No abstract available.
PubMed 21671894Lankiewicz MW, Hays J, Friedman KD, Tinkoff G, Blatt PM. Urgent reversal of warfarin with prothrombin complex concentrate. J Thromb Haemost. 2006 May;4(5):967-70. doi: 10.1111/j.1538-7836.2006.01815.x.
PubMed 16689743Makris M, Greaves M, Phillips WS, Kitchen S, Rosendaal FR, Preston EF. Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thromb Haemost. 1997 Mar;77(3):477-80.
PubMed 9065997Oden A, Fahlen M. Oral anticoagulation and risk of death: a medical record linkage study. BMJ. 2002 Nov 9;325(7372):1073-5. doi: 10.1136/bmj.325.7372.1073.
PubMed 12424167Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D'Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berrettini M, Musolesi S. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet. 1996 Aug 17;348(9025):423-8. doi: 10.1016/s0140-6736(96)01109-9.
PubMed 8709780A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. Ann Neurol. 1997 Dec;42(6):857-65. doi: 10.1002/ana.410420606.
PubMed 9403477van Aart L, Eijkhout HW, Kamphuis JS, Dam M, Schattenkerk ME, Schouten TJ, Ploeger B, Strengers PF. Individualized dosing regimen for prothrombin complex concentrate more effective than standard treatment in the reversal of oral anticoagulant therapy: an open, prospective randomized controlled trial. Thromb Res. 2006;118(3):313-20. doi: 10.1016/j.thromres.2005.08.005. Epub 2005 Sep 21.
PubMed 16182346Yasaka M, Sakata T, Minematsu K, Naritomi H. Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication. Thromb Res. 2002 Oct 1;108(1):25-30. doi: 10.1016/s0049-3848(02)00402-4.
PubMed 12586128Sarode R, Goldstein JN, Simonian G, Hinterberger D, Matveev D, Gareis M, Milling TJ Jr. Vitamin K Antagonist Reversal for Urgent Surgery Using 4-Factor Prothrombin Complex Concentrates: A Randomized Clinical Trial. JAMA Netw Open. 2024 Aug 1;7(8):e2424758. doi: 10.1001/jamanetworkopen.2024.24758.
PubMed 39088218
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Double-blind, Multicenter Study to Assess the Efficacy and Safety of OCTAPLEX, a Four-factor Prothrombin Complex Concentrate (4F-PCC), Compared to the 4F-PCC Beriplex® P/N (Kcentra), for the Reversal of Vitamin K Antagonist (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk.
- ClinicalTrials.gov ID
- NCT02740335
- Acronym / sponsor ID
- LEX-209
- Conditions
- Significant Bleeding Risk
- Keywords
- anticoagulant reversal, urgent surgery, invasive procedures, vitamin K, prothrombin complex concentrate, four-factor prothrombin complex concentrate (4F-PCC)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 208 participants (actual)
- Lead sponsor
- OctapharmaIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2017 (actual)
- Primary completion
- 23 Feb 2022 (actual)
- Study completion
- 23 Feb 2022 (actual)
- First posted
- 15 Apr 2016 (estimated)
- Results
- Posted 8 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under Vitamin K Antagonist (VKA) therapy with the need for urgent surgery with significant bleeding risk is clinically non-inferior to that Beriplex® P/N (Kcentra).
Detailed description
The primary objective of the study is to demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under Vitami n K Antagonist (VKA)therapy with the need for urgent surgery with significant bleeding risk is clinically non-inferior to that Beriplex® P/N (Kcentra).
The secondary objective of the study is to investigate the safety and tolerability of OCTAPLEX compared to Beriplex® P/N (Kcentra) in patients under Vitamin K Antagonist (VKA) therapy with the need for urgent surgery with significant bleeding risk.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Octaplex | Experimental | Drug: OctaplexParticipants to receive1 Octaplex infusion intravenously |
| Beriplex P/N (Kcentra) | Active comparator | Drug: Beriplex P/N (Kcentra)Participants to receive1 Kcentra infusions intravenously |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female patients at least 18 years of age.
- Patients currently on oral anticoagulation treatment with VKA of coumadin or warfarin type.
- Patients being admitted to the hospital or currently hospitalized where:
- Patients with an international normalized ratio (INR) of 2.0 or above at the time of decision to reverse the anticoagulation status.
- Patients who have given written informed consent and who are able and willing to comply with the procedures described in the study protocol.
Key exclusion criteria (14 listed)
- Patients with a life expectancy of less than 48 hours per physician's judgment (e.g. patients with a Glasgow Coma Scale equal to 3 or a Head Abbreviated Injury Score of 6, patients requiring continuous inotropic or pressor support, and patients whose status is post cardiac arrest).
- Patients for whom the planned surgery or procedure is commonly associated with a very low bleeding risk (e.g. catheter placement, gastroscopy).
- Patients with a history of thromboembolic events (TEEs), myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebrovascular accident, transient ischemic attack, severe peripheral vascular disease, or disseminated intravascular coagulation within 3 months of enrollment.
- Patients with a known congenital bleeding disorder.
- Patients with a known antiphospholipid antibody syndrome.
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 |
|---|---|---|
| OctaplexAlso: 4F PCC, 4 Factor PCC, 4 Factor Prothrombin Concentrate ComplexOCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min). | Drug | Octaplex |
| Beriplex P/N (Kcentra)Also: KcentraBeriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min). | Drug | Beriplex P/N (Kcentra) |
Primary outcome
Hemostatic Efficacy Rating by IEAB
Time frame: At the end of the surgery
Hemostatic Efficacy rated by the Independent Endpoint Adjudication Committee based on a 1 to 4 point hemostatic efficacy scale, taking into account blood loss and transfusion requirements in the context of the surgery. Hemostatic efficacy was assessed based on objective criteria in the categories 'excellent', 'good', 'moderate', or 'none'. Ratings of 'excellent' and 'good' were considered as 'effective' hemostasis, while ratings of 'moderate' and 'none' were considered as 'ineffective' hemostasis.
Dichotomous Hemostasis Success
Time frame: At the end of surgery
To demostrate clinical non-inferiority of treatment with Octaplex to treatment with Beriplex P/N (Kcentra) with respect to hemostatic success. Effective hemostatis includes Excellent and Good ratings, while Ineffective hemostasis includes Moderate, None and missing ratings from Global hemostatic efficacy observed by IEAB
6 secondary outcomes
Measuring of International Normalized Ratio (INR) to ≤ 1.5
Time frame: 30 minutes after the end of infusion
Coagulation Factor II Levels
Time frame: 30 minutes after the end of infusion
Coagulation Factor VII Levels
Time frame: 30 minutes after the end of infusion
Coagulation Factor IX Levels
Time frame: 30 minutes after the end of infusion
Coagulation Factor X Levels
Time frame: 30 minutes after the end of infusion
Number of Patients Requiring Red Blood Cells (RBC)
Time frame: At the end of surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16810012American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006 Jul;105(1):198-208. doi: 10.1097/00000542-200607000-00030. No abstract available.
- BackgroundCampbell P, Roberts G, Eaton V. Managing warfarin therapy in the community. Aust Prescriber 2001; 24:86-89.
- BackgroundCushman M, et al. Clinical Practice Guide on Antithrombotic Drug Dosing and Management of Antithrombotic Drug-Associated Bleeding Complications in Adults, American Society of Hematology, 2014.
- Background: PubMed 9857468Gohlke-Barwolf C. [Anticoagulation in surgery, after hemorrhagic complications and in pregnancy]. Z Kardiol. 1998;87 Suppl 4:56-62. German.
- Background: PubMed 25728933Goldstein JN, Refaai MA, Milling TJ Jr, Lewis B, Goldberg-Alberts R, Hug BA, Sarode R. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015 May 23;385(9982):2077-87. doi: 10.1016/S0140-6736(14)61685-8. Epub 2015 Feb 27.
- Background: PubMed 2281231Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of type I error probability spending functions. Stat Med. 1990 Dec;9(12):1439-45. doi: 10.1002/sim.4780091207.
- Background: PubMed 21671894Keeling D, Baglin T, Tait C, Watson H, Perry D, Baglin C, Kitchen S, Makris M; British Committee for Standards in Haematology. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol. 2011 Aug;154(3):311-24. doi: 10.1111/j.1365-2141.2011.08753.x. Epub 2011 Jun 14. No abstract available.
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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.
Wolfgang Frenzel study director
International Medical Monitor
86 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Octaplex and Beriplex P/N (Kcentra) in people with Significant Bleeding Risk, run by Octapharma at 86 sites in 11 countries.
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 8 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 86 sites in United States, Ukraine, Russia, Georgia, Romania and 6 more countries. 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 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?
Yes. Results are posted in the registry (first posted 8 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Hemostatic Efficacy Rating by IEAB (time frame: At the end of the surgery). 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?
On the ClinicalTrials.gov record for NCT02740335, which also lists 15 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 8 Mar 2023.