Cardiac ArrestPhase 1/2TIBOHCANCT02836340
TIBOHCA: Safety, Tolerability and Pharmacokinetics of 2-Iminobiotin (2-IB) After OHCA
A Phase 1/2 study testing 2-Iminobiotin in people with Cardiac Arrest and Hypoxic Ischemic Brain Injury, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Following successful cardiopulmonary resuscitation (CPR) after out of hospital cardiac arrest (OHCA), 50% of patients admitted to the Intensive Care Unit (ICU) die. As most patients die due to brain damage sustained during cardiac arrest and the subsequent reperfusion phase, effective neuroprotective strategies could… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Arrest, Hypoxic Ischemic Brain Injury
- What is being tested?
- 2-Iminobiotin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2016to Apr 2020
- Phase
- Phase 1/2
- 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
- Admission to the ICU after OHCA and successful CPR due to a cardiac cause
- Post anoxic coma on admission
- Ability to start study medication as soon as possible, but ultimately within 6h after OHCA via a central venous line
- Age 18 years or older
- Eligible for treatment with a target temperature management of 36⁰ C
Who cannot join
- No informed consent
- Known co-morbidity with a life expectancy of <6 months prior to cardiac arrest
- Women aged 49 or less
- Severe cognitive impairment (documented dementia) known prior to OHCA
- Inability to insert a central venous line
Trial locations and contacts
1 site in 1 country.
About this study
Official title: TIBOHCA: A Single-centre, Phase II Study to Evaluate the Safety, Tolerability and Pharmacokinetics of 2-Iminobiotin (2-IB) After Out of Hospital Cardiac Arrest
Following successful cardiopulmonary resuscitation (CPR) after out of hospital cardiac arrest (OHCA), 50% of patients admitted to the Intensive Care Unit (ICU) die. As most patients die due to brain damage sustained during cardiac arrest and the subsequent reperfusion phase, effective neuroprotective strategies could potentially improve outcome. In animal experiments, 2-Iminobiotin (2-IB), a selective neuronal and inducible nitric oxide synthase (NOS) inhibitor, given upon reperfusion has been shown to improve memory function. Since 2-IB has not shown any safety issues in preclinical and clinical studies. Before embarking on large studies with efficacy as primary endpoint, safety, tolerability and pharmacokinetics need to be established.
Objective: Evaluate short term safety and tolerability, and the pharmacokinetic properties of 2-IB in adult patients after OHCA.
Read more
Study design: Phase 2, single-centre, open-label, dose-escalation intervention study.
Study population: Three cohorts of eight evaluable patients admitted to the ICU after OHCA due to a cardiac cause.
Intervention:
The first eight patients will receive 0,055 mg/kg 2-IB every 4 hours intravenously, 6 times in total (part A). The second eight patients (cohort B) will receive 0,165 mg/kg every 4h iv, 6 times in total. The third eight patients (cohort C) will receive 0,5 mg/kg every 4h iv, 6 times in total. Medication has to be given as soon as possible and within 6h after OHCA. Escalation to the next dose level will only be done after pharmacokinetic analyses have performed, no relevant safety issues have been encountered, and the DSMB approves to move to the next dose level.
Main study parameters/endpoints:
Study parameters to evaluate short term safety and tolerability will be vital signs (heart frequency, blood pressure, cardiac ischemia) before and until 15 minutes after administration. (Serious) Adverse Events will be recorded on the ICU (up to 7 days) or until discharge from the ICU. For evaluation of the pharmacokinetics profile of 2-IB, 9 plasma samples will be analysed. Secondary parameters: Biochemical markers Neuron specific Enolase and s100b at 24h and 48h after start of study drug, occurrence of SAEs until 30 days after OHCA including death, long term term efficacy as determined by the Cerebral Performance Category (CPC), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) or the Telephone Interview Cognitive Status (TICS) scale at 30 days after OHCA.
Read the detailed description
Objective:
The primary objective of this study is to evaluate the short term safety and tolerability, and the pharmacokinetic properties of 2-IB when administered to adult patients after OHCA.
Study design:
A Phase 2, single-centre, open-label, dose-escalation intervention study.
Study population:
The study population will constitute of three cohorts of eight evaluable patients admitted to the ICU after CPR for OHCA due to a cardiac cause.
Intervention:
The first cohort of eight patients will receive 2-IB in a dose of 0,055 mg/kg/dose every 4 h iv, 6 times in total (part A). The second cohort of eight patients (cohort B) will receive an anticipated dose of 0,165 mg/kg/dose every 4h iv, 6 times in total ,and the third cohort of eight patients (cohort C) will receive an anticipated dose of 0,500 mg/kg/dose every 4h iv, 6 times in total. The first dose has to be given as soon as possible and within 6h after OHCA. Escalation to the next dose level will only be done after pharmacokinetic analyses have performed, no relevant safety issues have been encountered, and the DSMB approves to move to the next dose level.
Main study parameters/endpoints:
The main study parameters used for evaluating the short term safety and tolerability will be vital signs (heart frequency, blood pressure, cardiac ischemia) before and until 15 minutes after administration of the study drug and the need for intervention. Furthermore , biochemistry and haematology taken as part of standard clinical care will be assessed, and the occurrence of (Serious) Adverse Events ((S)AEs) until 7 days on the ICU or until discharge from the ICU, whichever occurs earlier.
For evaluation of the pharmacokinetics profile of 2-IB, 9 plasma samples will be analysed. Pharmacokinetic parameters to be determined will include Cmax, AUC, Tmax, t1/2, clearance (Cl), and volume of distribution (Vd).
Secondary parameters:
- Short term efficacy as determined by biochemical markers NSE and s100b at 24h and 48h after start of first infusion of study drug.
- Longer term safety as determined by the occurrence of SAEs until 30 days after OHCA including death.
- Longer term efficacy as determined by the Cerebral Performance Category (CPC), the Computer Assisted Mild Cognitive Impairment (CAMCI) score, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) or alternatively the Telefonisch Interview Cognitieve Status (TICS) scale (by telephone) at 30 days after OHCA.
- Conditions
- Cardiac Arrest, Hypoxic Ischemic Brain Injury
- Being tested
- 2-Iminobiotin
- Keywords
- neuroprotection
- Medical subject headings
- Heart Arrest, Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2-IminobiotinDrug
The Investigational Medicinal Product (IMP) under study is 2-IB, which is a biotin (Vitamin H or B7) analogue and a selective inhibitor of neuronal and inducible nitric oxide synthase (NOS).
| Study group | Role | What they receive |
|---|---|---|
| 2-Iminobiotin | Experimental | Increasing dosage of study drug Receives: Drug: 2-Iminobiotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with treatment related adverse events
Safety assessed as changes in heart frequency, blood pressure, cardiac ischemia (ST changes) during administration of study drug and 15 minutes thereafter and any interventions needed to maintain stability. Feasibility will be assessed by investigating whether treatment can be initiated succesfully within 6 hours after CPR.
Measured: 7 days
Secondary outcomes (3)
Cerebral Performance Category
Patients will visit the hospital or will be visited at home
Measured: 30 days
Plasma levels of 2-IB
During the administration period nine blood samples will be taken to investigate blood levels of 2-IB
Measured: 24hours
IQ-Code
Cognitive functioning, assessed by asking patient and caregiver
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2016 (estimated)
- Study startMay 2016
- Primary completionDec 2019
- Study completionApr 2020
Why it stopped: Inclusion of patients slow
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac ArrestStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. Marcus J. Schultz, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Janneke Horn, MD, PhD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02836340
- Sponsor's protocol ID
- AMC-TIBOHCA
- Acronym
- TIBOHCA
- Status last verified
- Feb 2021
- First submitted
- 1 Jun 2016
- Last updated
- 18 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TIBOHCA: A Single-centre, Phase II Study to Evaluate the Safety, Tolerability and Pharmacokinetics of 2-Iminobiotin (2-IB) After Out of Hospital Cardiac Arrest
- ClinicalTrials.gov ID
- NCT02836340
- Acronym / sponsor ID
- TIBOHCA / AMC-TIBOHCA
- Conditions
- Cardiac Arrest, Hypoxic Ischemic Brain Injury
- Keywords
- neuroprotection
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inclusion of patients slow
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- May 2016 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Apr 2020 (actual)
- First posted
- 19 Jul 2016 (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.
Following successful cardiopulmonary resuscitation (CPR) after out of hospital cardiac arrest (OHCA), 50% of patients admitted to the Intensive Care Unit (ICU) die. As most patients die due to brain damage sustained during cardiac arrest and the subsequent reperfusion phase, effective neuroprotective strategies could potentially improve outcome. In animal experiments, 2-Iminobiotin (2-IB), a selective neuronal and inducible nitric oxide synthase (NOS) inhibitor, given upon reperfusion has been shown to improve memory function. Since 2-IB has not shown any safety issues in preclinical and clinical studies. Before embarking on large studies with efficacy as primary endpoint, safety, tolerability and pharmacokinetics need to be established.
Objective: Evaluate short term safety and tolerability, and the pharmacokinetic properties of 2-IB in adult patients after OHCA.
Study design: Phase 2, single-centre, open-label, dose-escalation intervention study.
Study population: Three cohorts of eight evaluable patients admitted to the ICU after OHCA due to a cardiac cause.
Intervention:
The first eight patients will receive 0,055 mg/kg 2-IB every 4 hours intravenously, 6 times in total (part A). The second eight patients (cohort B) will receive 0,165 mg/kg every 4h iv, 6 times in total. The third eight patients (cohort C) will receive 0,5 mg/kg every 4h iv, 6 times in total. Medication has to be given as soon as possible and within 6h after OHCA. Escalation to the next dose level will only be done after pharmacokinetic analyses have performed, no relevant safety issues have been encountered, and the DSMB approves to move to the next dose level.
Main study parameters/endpoints:
Study parameters to evaluate short term safety and tolerability will be vital signs (heart frequency, blood pressure, cardiac ischemia) before and until 15 minutes after administration. (Serious) Adverse Events will be recorded on the ICU (up to 7 days) or until discharge from the ICU. For evaluation of the pharmacokinetics profile of 2-IB, 9 plasma samples will be analysed. Secondary parameters: Biochemical markers Neuron specific Enolase and s100b at 24h and 48h after start of study drug, occurrence of SAEs until 30 days after OHCA including death, long term term efficacy as determined by the Cerebral Performance Category (CPC), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) or the Telephone Interview Cognitive Status (TICS) scale at 30 days after OHCA.
Detailed description
Objective:
The primary objective of this study is to evaluate the short term safety and tolerability, and the pharmacokinetic properties of 2-IB when administered to adult patients after OHCA.
Study design:
A Phase 2, single-centre, open-label, dose-escalation intervention study.
Study population:
The study population will constitute of three cohorts of eight evaluable patients admitted to the ICU after CPR for OHCA due to a cardiac cause.
Intervention:
The first cohort of eight patients will receive 2-IB in a dose of 0,055 mg/kg/dose every 4 h iv, 6 times in total (part A). The second cohort of eight patients (cohort B) will receive an anticipated dose of 0,165 mg/kg/dose every 4h iv, 6 times in total ,and the third cohort of eight patients (cohort C) will receive an anticipated dose of 0,500 mg/kg/dose every 4h iv, 6 times in total. The first dose has to be given as soon as possible and within 6h after OHCA. Escalation to the next dose level will only be done after pharmacokinetic analyses have performed, no relevant safety issues have been encountered, and the DSMB approves to move to the next dose level.
Main study parameters/endpoints:
The main study parameters used for evaluating the short term safety and tolerability will be vital signs (heart frequency, blood pressure, cardiac ischemia) before and until 15 minutes after administration of the study drug and the need for intervention. Furthermore , biochemistry and haematology taken as part of standard clinical care will be assessed, and the occurrence of (Serious) Adverse Events ((S)AEs) until 7 days on the ICU or until discharge from the ICU, whichever occurs earlier.
For evaluation of the pharmacokinetics profile of 2-IB, 9 plasma samples will be analysed. Pharmacokinetic parameters to be determined will include Cmax, AUC, Tmax, t1/2, clearance (Cl), and volume of distribution (Vd).
Secondary parameters:
- Short term efficacy as determined by biochemical markers NSE and s100b at 24h and 48h after start of first infusion of study drug.
- Longer term safety as determined by the occurrence of SAEs until 30 days after OHCA including death.
- Longer term efficacy as determined by the Cerebral Performance Category (CPC), the Computer Assisted Mild Cognitive Impairment (CAMCI) score, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) or alternatively the Telefonisch Interview Cognitieve Status (TICS) scale (by telephone) at 30 days after OHCA.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 2-Iminobiotin | Experimental | Drug: 2-IminobiotinIncreasing dosage of study drug |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Admission to the ICU after OHCA and successful CPR due to a cardiac cause
- Post anoxic coma on admission
- Ability to start study medication as soon as possible, but ultimately within 6h after OHCA via a central venous line
- Age 18 years or older
- Eligible for treatment with a target temperature management of 36⁰ C
Key exclusion criteria (5 listed)
- No informed consent
- Known co-morbidity with a life expectancy of <6 months prior to cardiac arrest
- Women aged 49 or less
- Severe cognitive impairment (documented dementia) known prior to OHCA
- Inability to insert a central venous line
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 |
|---|---|---|
| 2-IminobiotinThe Investigational Medicinal Product (IMP) under study is 2-IB, which is a biotin (Vitamin H or B7) analogue and a selective inhibitor of neuronal and inducible nitric oxide synthase (NOS). | Drug | 2-Iminobiotin |
Primary outcome
Number of patients with treatment related adverse events
Time frame: 7 days
Safety assessed as changes in heart frequency, blood pressure, cardiac ischemia (ST changes) during administration of study drug and 15 minutes thereafter and any interventions needed to maintain stability. Feasibility will be assessed by investigating whether treatment can be initiated succesfully within 6 hours after CPR.
3 secondary outcomes
Cerebral Performance Category
Time frame: 30 days
Plasma levels of 2-IB
Time frame: 24hours
IQ-Code
Time frame: 30 days
Results and safety
The study was stopped early (reason given: Inclusion of patients slow). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2021.
- Individual participant dataSharing planned: No
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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.
Janneke Horn, MD, PhD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 2-Iminobiotin in people with Cardiac Arrest and Hypoxic Ischemic Brain Injury, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) 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 5 inclusion and 5 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: stopped early, as of the sponsor's last update on 18 Feb 2021. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: Inclusion of patients slow). Results are not available in the source record.
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?
Number of patients with treatment related adverse events (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Feb 2021.