Intracranial HemorrhagesPhase 4INCHNCT00928915
International Normalized Ratio (INR) Normalization in Coumadin Associated Intracerebral Haemorrhage
A Phase 4 study testing Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP) in people with Intracranial Hemorrhages, run by Heidelberg University at 1 site in Germany.
Trial summary
Intracerebral haemorrhage (ICH) is the most feared complication in patients on vitamin K antagonists (VKA). VKA related ICH occurs 8-10 times more frequently and the mortality is 2 times higher than in non-anticoagulated patients. Mortality may rise up to 67%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracranial Hemorrhages
- What is being tested?
- Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2009to Jan 2015
- Phase
- Phase 4
- 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
- Spontaneous ICH (intraparenchymal), subdural hematoma (SDH) diagnosed by CT scanning ≤ 12 hours after onset of symptoms. In case of unknown time of symptom onset: time between last seen in healthy condition and first CCT ≤ 12 hours.
- Therapy receiving vitamin K antagonists (VKA)
- International Normalized Ratio (INR) ≥ 2
- Signed informed consent form, or signed informed consent by a legal representative, judicial consent in cases where no legal representative is available in time, or consent of an independent physician familiar with the indication in cases where the first three possibilities can not be realized.
Who cannot join
- Patients with ICH not related to vitamin-K antagonist therapy or
- Patients with secondary ICH related to infarction, hemophilia or other coagulopathy, tumor, hemorrhagic infarction, cerebrovenous thrombosis, aneurysm, arteriovenous malformations (AVM) or severe trauma
- Deep Coma (GCS ≤ 5) at the time of admission or before intubation if intubated outside the hospital
- Known previous disability (mRS > 2 before stroke occurred)
- Acute myocardial ischemia, acute septicemia, acute crush injury, any history of acute hemorrhagic disseminated intravascular coagulation, acute thrombotic stroke
- Known history of intermittent claudication
Show all 19Show fewer
- Known recent thrombotic event < 30 days
- Acute or known congestive heart failure (NYHA III, IV)
- Pulmonary edema
- Known liver failure (child-pugh-score C)
- Known alcohol or other drug abuse
- Known active malignant disease
- Known thrombocytopenia (platelets <50,000/µL), hemorrhagic diathesis (primary defects of coagulation, fibrinolysis, platelets)
- History of hypersensitivity to the investigational products or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational product
- Known allergy to heparin or history of heparin induced thrombocytopenia.
- Pregnancy and lactation
- Concomitant use of antithrombotic (with PTT > 1.5 of normal PTT), thrombolytic treatment.
- Use of aspirin, clopidogrel or dipyridamole or combinations thereof (e.g. Aggrenox®) is not an exclusion criterion. These drugs should be discontinued and not restarted earlier than 24 hours after normalization of INR if indicated.
- Previous participation in this trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multicenter, Prospective Randomized Trial on the Use of Prothrombin Complex and Fresh Frozen Plasma in Patients With Intracerebral Hemorrhage Related to Vitamin K Antagonists
Intracerebral haemorrhage (ICH) is the most feared complication in patients on vitamin K antagonists (VKA). VKA related ICH occurs 8-10 times more frequently and the mortality is 2 times higher than in non-anticoagulated patients. Mortality may rise up to 67%. The higher mortality rate may in part be due to the higher rate of haematoma expansion (HE) over a longer period after symptom onset. International guidelines recommend treatment of VKA-ICH with prothrombin complex (PCC) or fresh-frozen plasma (FFP) both in combination with Vitamin-K. But these recommendations are not based on randomized controlled trials. It is known that these drugs lower the INR, and thus it is assumed that normalization of coagulopathy may lead to haemostasis and reduction of HE. Safety and efficacy of these treatments have never been studied in a prospective controlled trial.
The investigators' questions are: How potent are PCC and FFP in normalization of the INR? What is the safety profile of each of these drugs?
- Conditions
- Intracranial Hemorrhages
- Being tested
- Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)
- Keywords
- Intracranial Hemorrhages, Vitamin-K antagonist, Hemostatic treatment, Prothrombin complex, Fresh frozen plasma, Intracranial Hemorrhages related to vitamin-K antagonist
- Medical subject headings
- Intracranial Hemorrhages
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)Drug
intravenous, repeated until INR ≤ 1.2
| Study group | Role | What they receive |
|---|---|---|
| Prothrombin complex concentrate (PCC) | Experimental | intravenously, 30 IU/kg Receives: Drug: Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP) |
| Fresh frozen plasma (FFP) | Experimental | intravenously, 20ml/kg Receives: Drug: Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
INR ≤ 1.2 within 3 hours after start of drug infusion
Measured: 3 hours
Secondary outcomes (3)
Safety: Number of thromboembolic events
Measured: 90 days
Efficacy: Percentage of volume increase
Measured: 24 hours
Clinical outcome
Measured: day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2009 (estimated)
- Study startJul 2009
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Intracranial HemorrhagesStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thorsten Steiner, Heidelberg University
- Investigators
- Thorsten Steiner, MR, PhD, MME, Principal investigator, Department of Neurology, Heidelberg University Hospital Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00928915
- Sponsor's protocol ID
- AFmu-344/2008
- Other IDs
- EUDRAT 2008-005653-37
- Acronym
- INCH
- Status last verified
- Oct 2016
- First submitted
- 25 Jun 2009
- Last updated
- 26 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Steiner T, Griebe M, Ivandic B, et al. Multicenter, prospective randomized trial on the use of prothrombin complex and fresh frozen plasma to normalize the INR in patients with coumadine related intracerebral hemorrhage related to vitamin K antagonists - The INCH-trial. Cerebovascular Disease 2009;27:185
Steiner T, Freiberger A, Griebe M, Husing J, Ivandic B, Kollmar R, Pfefferkorn T, Wartenberg KE, Weimar C, Hennerici M, Poli S. International normalised ratio normalisation in patients with coumarin-related intracranial haemorrhages--the INCH trial: a randomised controlled multicentre trial to compare safety and preliminary efficacy of fresh frozen plasma and prothrombin complex--study design and protocol. Int J Stroke. 2011 Jun;6(3):271-7. doi: 10.1111/j.1747-4949.2010.00560.x. Epub 2011 Jan 10.
PubMed 21557816Steiner T, Poli S, Griebe M, Husing J, Hajda J, Freiberger A, Bendszus M, Bosel J, Christensen H, Dohmen C, Hennerici M, Kollmer J, Stetefeld H, Wartenberg KE, Weimar C, Hacke W, Veltkamp R. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurol. 2016 May;15(6):566-73. doi: 10.1016/S1474-4422(16)00110-1. Epub 2016 Apr 11.
PubMed 27302126Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD005951. doi: 10.1002/14651858.CD005951.pub5.
PubMed 37870112
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Prospective Randomized Trial on the Use of Prothrombin Complex and Fresh Frozen Plasma in Patients With Intracerebral Hemorrhage Related to Vitamin K Antagonists
- ClinicalTrials.gov ID
- NCT00928915
- Acronym / sponsor ID
- INCH / AFmu-344/2008
- Conditions
- Intracranial Hemorrhages
- Keywords
- Intracranial Hemorrhages, Vitamin-K antagonist, Hemostatic treatment, Prothrombin complex, Fresh frozen plasma, Intracranial Hemorrhages related to vitamin-K antagonist
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Study start
- Jul 2009
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 26 Jun 2009 (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.
Intracerebral haemorrhage (ICH) is the most feared complication in patients on vitamin K antagonists (VKA). VKA related ICH occurs 8-10 times more frequently and the mortality is 2 times higher than in non-anticoagulated patients. Mortality may rise up to 67%. The higher mortality rate may in part be due to the higher rate of haematoma expansion (HE) over a longer period after symptom onset. International guidelines recommend treatment of VKA-ICH with prothrombin complex (PCC) or fresh-frozen plasma (FFP) both in combination with Vitamin-K. But these recommendations are not based on randomized controlled trials. It is known that these drugs lower the INR, and thus it is assumed that normalization of coagulopathy may lead to haemostasis and reduction of HE. Safety and efficacy of these treatments have never been studied in a prospective controlled trial.
The investigators' questions are: How potent are PCC and FFP in normalization of the INR? What is the safety profile of each of these drugs?
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prothrombin complex concentrate (PCC) | Experimental | Drug: Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)intravenously, 30 IU/kg |
| Fresh frozen plasma (FFP) | Experimental | Drug: Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)intravenously, 20ml/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Spontaneous ICH (intraparenchymal), subdural hematoma (SDH) diagnosed by CT scanning ≤ 12 hours after onset of symptoms. In case of unknown time of symptom onset: time between last seen in healthy condition and first CCT ≤ 12 hours.
- Therapy receiving vitamin K antagonists (VKA)
- International Normalized Ratio (INR) ≥ 2
- Signed informed consent form, or signed informed consent by a legal representative, judicial consent in cases where no legal representative is available in time, or consent of an independent physician familiar with the indication in cases where the first three possibilities can not be realized.
Key exclusion criteria (19 listed)
- Patients with ICH not related to vitamin-K antagonist therapy or
- Patients with secondary ICH related to infarction, hemophilia or other coagulopathy, tumor, hemorrhagic infarction, cerebrovenous thrombosis, aneurysm, arteriovenous malformations (AVM) or severe trauma
- Deep Coma (GCS ≤ 5) at the time of admission or before intubation if intubated outside the hospital
- Known previous disability (mRS > 2 before stroke occurred)
- Acute myocardial ischemia, acute septicemia, acute crush injury, any history of acute hemorrhagic disseminated intravascular coagulation, acute thrombotic stroke
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 |
|---|---|---|
| Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)intravenous, repeated until INR ≤ 1.2 | Drug | Fresh frozen plasma (FFP), Prothrombin complex concentrate (PCC) |
Primary outcome
INR ≤ 1.2 within 3 hours after start of drug infusion
Time frame: 3 hours
3 secondary outcomes
Safety: Number of thromboembolic events
Time frame: 90 days
Efficacy: Percentage of volume increase
Time frame: 24 hours
Clinical outcome
Time frame: day 90
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 26 Oct 2016.
- BackgroundSteiner T, Griebe M, Ivandic B, et al. Multicenter, prospective randomized trial on the use of prothrombin complex and fresh frozen plasma to normalize the INR in patients with coumadine related intracerebral hemorrhage related to vitamin K antagonists - The INCH-trial. Cerebovascular Disease 2009;27:185
- Background: PubMed 21557816Steiner T, Freiberger A, Griebe M, Husing J, Ivandic B, Kollmar R, Pfefferkorn T, Wartenberg KE, Weimar C, Hennerici M, Poli S. International normalised ratio normalisation in patients with coumarin-related intracranial haemorrhages--the INCH trial: a randomised controlled multicentre trial to compare safety and preliminary efficacy of fresh frozen plasma and prothrombin complex--study design and protocol. Int J Stroke. 2011 Jun;6(3):271-7. doi: 10.1111/j.1747-4949.2010.00560.x. Epub 2011 Jan 10.
- Results publication: PubMed 27302126Steiner T, Poli S, Griebe M, Husing J, Hajda J, Freiberger A, Bendszus M, Bosel J, Christensen H, Dohmen C, Hennerici M, Kollmer J, Stetefeld H, Wartenberg KE, Weimar C, Hacke W, Veltkamp R. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurol. 2016 May;15(6):566-73. doi: 10.1016/S1474-4422(16)00110-1. Epub 2016 Apr 11.
- Derived from this study: PubMed 37870112Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD005951. doi: 10.1002/14651858.CD005951.pub5.
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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.
Thorsten Steiner, MR, PhD, MME principal investigator
Department of Neurology, Heidelberg University Hospital Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP) in people with Intracranial Hemorrhages, run by Heidelberg University at 1 site in Germany.
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 19 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 26 Oct 2016. 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 Germany. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
INR ≤ 1.2 within 3 hours after start of drug infusion (time frame: 3 hours). 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 NCT00928915, which also lists 4 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 26 Oct 2016.