Heparin Overdose of Undetermined IntentNCT05509647
Unfractionated Heparin in COVID-19 and Non-COVID-19 Patients
An observational study of Heparin Overdose of Undetermined Intent and COVID-19, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
The majority of ICU patients with COVID-19 show profound activation of coagulation, potentially resulting in thromboembolic events. In the treatment of these thromboembolic events it seemed that very high dosages of unfractionated heparin were necessary to achieve therapeutic values of aPTT and anti-Xa levels. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heparin Overdose of Undetermined Intent, COVID-19
- What is being tested?
- Unfractionated heparin
- How many people
- 1,500 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jan 2014to 1 Oct 2022
- Phase
- Observational
- 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
Study population: Patients admitted to the ICU in the above mentioned periods of time and in need for unfractionated heparin treatment are eligible to participate in the study. There is no selection bias: all patients fulfilling the entry criteria will be included.
Who may be able to join
- Covid-19 disease proven by PCR of nose- or airway sample
- Age ≥ 18 years
- Admitted to the ICU from the 15th of March 2020 until 1st of January 2022
- Treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml
- Age ≥ 18 years
- Admitted to the ICU between the 1st of January 2014 and 1st of January 2020
- Treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml
Who cannot join
- Treatment with anticoagulants other than UFH or fibrinolytics
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Leiden University Medical Centre
Leiden, South Holland, 2333ZA
About this study
Official title: Unfractionated Heparin in COVID-19 and Non-COVID-19 Patients - an Observational Study.
The majority of ICU patients with COVID-19 show profound activation of coagulation, potentially resulting in thromboembolic events. In the treatment of these thromboembolic events it seemed that very high dosages of unfractionated heparin were necessary to achieve therapeutic values of aPTT and anti-Xa levels. The aim of this study is to explore whether heparin dosages are higher in COVID-19 patients compared to non-COVID-19 patients, to determine the correlation between aPTT and anti-Xa values and to explore possible causes for non-correlating aPTT and anti-Xa, including CRP and AT plasma levels.
Read the detailed description
CoVID-19 is a viral disease caused by SARS-CoV-2 virus that may affect many organ systems. Patients with severe disease almost invariably have profound pulmonary inflammation and may require mechanical ventilation and prolonged ICU admission. Mortality in ICU patients may be up to 50%. In the majority of patients with CoVID-19 in the ICU, profound activation of coagulation is present as reflected by d-dimer levels up to 20.000 mg/L or higher. Patients with proven pulmonary thrombosis are commonly treated with unfractionated heparin (UFH). Typically, it seemed that very high dosages of UFH were necessary to achieve therapeutic values of aPTT and anti-Xa levels in COVID-19 patients. Though, the question remains whether dosages given in COVID-19 patients were indeed extravagant compared to non-COVID-19 patients and what potential causes of these high dosages might be. Earlier research already implied that APTT, which is a primarily used parameter to dose UFH, is not accurate and rather anti-Xa levels should be used. Other potential reasons for the high doses are that COVID-19 patients show signs of heparin resistance, possible due to high inflammation parameters. As overdosing of heparin can lead to serious bleeding complications, more understanding on heparin dosage, e.g. parameters to rely on and potential influencing factors, in COVID-19 patients is needed. The primary objective of this study is to determine whether heparin dosages are higher in COVID-19 patients compared to non COVID-19 patients. The secondary objective is to determine the correlation between aPTT and anti-Xa values and to explore possible causes for non-correlating aPTT and anti-Xa, including CRP and AT plasma levels.
- Conditions
- Heparin Overdose of Undetermined Intent, COVID-19
- Being tested
- Unfractionated heparin
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Unfractionated heparinDrug
Patients are treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa levels of 0.3-0.7 iE/ml
| Study group | Role | What they receive |
|---|---|---|
| Covid-19 patients | Adult patients treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml. All patients have Covid-19 proven by PCR or nose- or airway swab. Patients admitted to the ICU from the 15th of March 2020 until January 2022. Receives: Drug: Unfractionated heparin | |
| non-COVID-19 patients | Adult patients treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml. Patients admitted to the ICU between the 1st of January 2014 and the 1st of January 2020 are included. Receives: Drug: Unfractionated heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heparin dosage
To determine whether heparin dosages are higher in COVID-19 patients compared to non COVID-19 patients.
Measured: Until end of heparin therapy or ICU discharge, whatever comes first.
Secondary outcomes (3)
Correlation between aPTT and anti-Xa values
To explore possible causes for non-correlating aPTT and Anti-Xa levels
Measured: Until end of heparin therapy or ICU discharge, whatever comes first.
Correlation between non-correlating aPTT and Anti-Xa levels and CRP
To explore possible causes for non-correlating aPTT and Anti-Xa levels
Measured: Until end of heparin therapy or ICU discharge, whatever comes first.
Correlation between non-correlating aPTT and Anti-Xa levels and AT plasma levels
To explore possible causes for non-correlating aPTT and Anti-Xa levels
Measured: Until end of heparin therapy or ICU discharge, whatever comes first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2022
- Study start1 Jan 2014
- Primary completion1 Oct 2022
- Study completion1 Oct 2022
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 Heparin Overdose of Undetermined IntentStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, edejonge, Leiden University Medical Center
- Investigators
- Evert de Jonge, MD, PhD, Principal investigator, Leiden University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05509647
- Sponsor's protocol ID
- CoCo 2022-020
- Status last verified
- Oct 2023
- First submitted
- 25 Apr 2022
- Last updated
- 5 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
PubMed 32105632Thachil J, Tang N, Gando S, Falanga A, Levi M, Clark C, Iba T, Cattaneo M. Type and dose of heparin in Covid-19: Reply. J Thromb Haemost. 2020 Aug;18(8):2063-2064. doi: 10.1111/jth.14870. Epub 2020 May 11. No abstract available.
PubMed 32329221Arachchillage DRJ, Kamani F, Deplano S, Banya W, Laffan M. Should we abandon the APTT for monitoring unfractionated heparin? Thromb Res. 2017 Sep;157:157-161. doi: 10.1016/j.thromres.2017.07.006. Epub 2017 Jul 6.
PubMed 28759760White D, MacDonald S, Bull T, Hayman M, de Monteverde-Robb R, Sapsford D, Lavinio A, Varley J, Johnston A, Besser M, Thomas W. Heparin resistance in COVID-19 patients in the intensive care unit. J Thromb Thrombolysis. 2020 Aug;50(2):287-291. doi: 10.1007/s11239-020-02145-0.
PubMed 32445064
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unfractionated Heparin in COVID-19 and Non-COVID-19 Patients - an Observational Study.
- ClinicalTrials.gov ID
- NCT05509647
- Acronym / sponsor ID
- CoCo 2022-020
- Conditions
- Heparin Overdose of Undetermined Intent, COVID-19
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,500 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- 1 Jan 2014 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 1 Oct 2022 (actual)
- First posted
- 22 Aug 2022 (actual)
- 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 majority of ICU patients with COVID-19 show profound activation of coagulation, potentially resulting in thromboembolic events. In the treatment of these thromboembolic events it seemed that very high dosages of unfractionated heparin were necessary to achieve therapeutic values of aPTT and anti-Xa levels. The aim of this study is to explore whether heparin dosages are higher in COVID-19 patients compared to non-COVID-19 patients, to determine the correlation between aPTT and anti-Xa values and to explore possible causes for non-correlating aPTT and anti-Xa, including CRP and AT plasma levels.
Detailed description
CoVID-19 is a viral disease caused by SARS-CoV-2 virus that may affect many organ systems. Patients with severe disease almost invariably have profound pulmonary inflammation and may require mechanical ventilation and prolonged ICU admission. Mortality in ICU patients may be up to 50%. In the majority of patients with CoVID-19 in the ICU, profound activation of coagulation is present as reflected by d-dimer levels up to 20.000 mg/L or higher. Patients with proven pulmonary thrombosis are commonly treated with unfractionated heparin (UFH). Typically, it seemed that very high dosages of UFH were necessary to achieve therapeutic values of aPTT and anti-Xa levels in COVID-19 patients. Though, the question remains whether dosages given in COVID-19 patients were indeed extravagant compared to non-COVID-19 patients and what potential causes of these high dosages might be. Earlier research already implied that APTT, which is a primarily used parameter to dose UFH, is not accurate and rather anti-Xa levels should be used. Other potential reasons for the high doses are that COVID-19 patients show signs of heparin resistance, possible due to high inflammation parameters. As overdosing of heparin can lead to serious bleeding complications, more understanding on heparin dosage, e.g. parameters to rely on and potential influencing factors, in COVID-19 patients is needed. The primary objective of this study is to determine whether heparin dosages are higher in COVID-19 patients compared to non COVID-19 patients. The secondary objective is to determine the correlation between aPTT and anti-Xa values and to explore possible causes for non-correlating aPTT and anti-Xa, including CRP and AT plasma levels.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Covid-19 patients | – | Drug: Unfractionated heparinAdult patients treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml. All patients have Covid-19 proven by PCR or nose- or airway swab. Patients admitted to the ICU from the 15th of March 2020 until January 2022. |
| non-COVID-19 patients | – | Drug: Unfractionated heparinAdult patients treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml. Patients admitted to the ICU between the 1st of January 2014 and the 1st of January 2020 are included. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients admitted to the ICU in the above mentioned periods of time and in need for unfractionated heparin treatment are eligible to participate in the study. There is no selection bias: all patients fulfilling the entry criteria will be included.
Key inclusion criteria (7 listed)
- Covid-19 disease proven by PCR of nose- or airway sample
- Age ≥ 18 years
- Admitted to the ICU from the 15th of March 2020 until 1st of January 2022
- Treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml
- Age ≥ 18 years
Key exclusion criteria (1 listed)
- Treatment with anticoagulants other than UFH or fibrinolytics
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 |
|---|---|---|
| Unfractionated heparinPatients are treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa levels of 0.3-0.7 iE/ml | Drug | Covid-19 patients, non-COVID-19 patients |
Primary outcome
Heparin dosage
Time frame: Until end of heparin therapy or ICU discharge, whatever comes first.
To determine whether heparin dosages are higher in COVID-19 patients compared to non COVID-19 patients.
3 secondary outcomes
Correlation between aPTT and anti-Xa values
Time frame: Until end of heparin therapy or ICU discharge, whatever comes first.
Correlation between non-correlating aPTT and Anti-Xa levels and CRP
Time frame: Until end of heparin therapy or ICU discharge, whatever comes first.
Correlation between non-correlating aPTT and Anti-Xa levels and AT plasma levels
Time frame: Until end of heparin therapy or ICU discharge, whatever comes first.
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 5 Oct 2023.
- Background: PubMed 32105632Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.
- Background: PubMed 32329221Thachil J, Tang N, Gando S, Falanga A, Levi M, Clark C, Iba T, Cattaneo M. Type and dose of heparin in Covid-19: Reply. J Thromb Haemost. 2020 Aug;18(8):2063-2064. doi: 10.1111/jth.14870. Epub 2020 May 11. No abstract available.
- Background: PubMed 28759760Arachchillage DRJ, Kamani F, Deplano S, Banya W, Laffan M. Should we abandon the APTT for monitoring unfractionated heparin? Thromb Res. 2017 Sep;157:157-161. doi: 10.1016/j.thromres.2017.07.006. Epub 2017 Jul 6.
- Background: PubMed 32445064White D, MacDonald S, Bull T, Hayman M, de Monteverde-Robb R, Sapsford D, Lavinio A, Varley J, Johnston A, Besser M, Thomas W. Heparin resistance in COVID-19 patients in the intensive care unit. J Thromb Thrombolysis. 2020 Aug;50(2):287-291. doi: 10.1007/s11239-020-02145-0.
- Individual participant dataSharing planned: No
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.
Evert de Jonge, MD, PhD principal investigator
Leiden University Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heparin Overdose of Undetermined Intent and COVID-19, run by Leiden University Medical Center at 1 site in Netherlands.
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 1 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 5 Oct 2023. 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 Netherlands. 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.
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?
Heparin dosage (time frame: Until end of heparin therapy or ICU discharge, whatever comes first.). 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 NCT05509647, 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 5 Oct 2023.