Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02836340 |
| Other study ID # |
AMC-TIBOHCA |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
May 2016 |
| Est. completion date |
April 2020 |
Study information
| Verified date |
February 2021 |
| Source |
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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 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.
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:
1. Short term efficacy as determined by biochemical markers NSE and s100b at 24h and 48h
after start of first infusion of study drug.
2. Longer term safety as determined by the occurrence of SAEs until 30 days after OHCA
including death.
3. 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.
