Acute Peripheral Arterial OcclusionPhase 2NCT01222117
A Study of Intra-thrombus Plasmin (Human) In Acute Peripheral Arterial Occlusion
A Phase 2 study testing Plasmin and Plasminogen Activator in people with Acute Peripheral Arterial Occlusion, run by Grifols Therapeutics LLC at 39 sites in 12 countries.
Trial summary
The primary purpose of this Phase 2 study is to optimize Plasmin delivery by comparing different delivery regimens in patients with peripheral arterial occlusion. The study includes a blinded plasminogen activator treatment group and a blinded plasminogen activator placebo group. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Peripheral Arterial Occlusion
- What is being tested?
- Plasmin and Plasminogen Activator
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 174 participants
- Where
- 39 sitesin 12 countries
- Study dates
- Dec 2010to Jan 2016
- Phase
- Phase 2
- 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
- Unilateral limb ischemia - Society of Vascular Surgery Categories I and IIa
- Onset of symptoms less than or equal to 14 days
- Thrombosed infrainguinal bypass graft or native artery
- Diagnosis by arteriography of occlusive thrombus in graft or artery
- Ability to embed the infusion catheter into the thrombus
- Women of childbearing potential must use contraception and have a negative pregnancy test
Who cannot join
- Any medical or social condition that may interfere with study participation
- Women who are pregnant or lactating
- Hemorrhagic stroke history
- Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack) within one year
- Intracranial or spinal neurosurgery, or severe intracranial trauma in the last 3 months
- Major surgery, organ biopsy, or major trauma within the past 10 days
Show all 24Show fewer
- Lumbar puncture or non-compressible arterial puncture in the past 10 days
- Intraocular surgery within the past 10 days
- Active gastrointestinal or organ bleeding
- Uncontrolled arterial hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg)
- Known intracranial neoplasm, aneurysm, or arteriovenous malformation
- Current bleeding diathesis
- Platelet count <75 x 10e9/L
- Active graft infection
- Occlusion occurred within one month of synthetic graft placement
- Occlusion occurred within 6 months of autologous graft placement
- A sequential composite graft with dual outflows to correct multiple occlusions
- Medically unable to tolerate an open vascular procedure
- Known prothrombotic state
- Hemoglobin <10.0 g/dL
- Impaired renal function or renal disease that constitutes a contraindication to contrast angiography, including creatinine >2.0 mg/dL
- Treatment with a full dose plasminogen activator (PA) within the last 48 hours
- Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within the past 5 days
- Treatment with oral anticoagulants, and with an international normalized ratio of >1.7
Trial locations and contacts
39 sites in 12 countries.
39 sites in 12 countries
Poland6 sites
Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu
Bytom
Malopolskie Centrum Sercowo-Naczyniowe PAKS American Heart of Poland Sp. z o.o
Chrzanów
Uniwersyleckie Centrum Kliniczne
Gdansk
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
Poznan
Zaklad Opieki Zdrowonej Ministerstwa Spraw Wewnetrznych i Administracji w Poznaniu
Poznan
Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
Szczecin
Czechia5 sites
Vascular Centre Vitkovicka Nemocnice
Ostrava - Vitkovice
Cevni Chirurgie, Nemocnice Na Homolce
Prague
IKEM, Kardiologicka klinika
Prague
University Hospital Kralovske Vinobrady
Prague
Chirurgicka klinika IPVZ
Ústí nad Labem
Belgium4 sites
Erasme Hospital, Brussels
Brussels, 1070
University Hospital Antwerp
Edegem
Ziekenhuis Oost Limburg, Campus St. Jan
Genk, Limburg, 3600
Chirurgie UZ Leuven
Leuven
Peru4 sites
Centro de Investigación y Atención Cardiovascular
Lima
Hospital Nacional Edgardo Rebagliati Martins
Lima
Hospital Nacional Guillermo Almenara Irigoyen-EsSalud
Lima
Instituto Neuro Cardiovascular de las Americas
Lima
Romania4 sites
Institutul de Urgenta pentru Boli Cardiovasculare "Prof.Dr.C.C.Iliescu"
Bucharest
Institutul Inimii "Nicolae Stancioiu" Cluj-Napoca
Cluj-Napoca
Inst.de Boli Cardiovasculare "Prof.I.M.Georgescu" Iasi
Iași
Institutul de Boli Cardiovasculare si Transplant Mures
Târgu Mureş
Serbia4 sites
Institut za kardiovaskularne bolesti Dedinje
Belgrade, 11040
Klinicki Centar Srbije
Belgrade
Klinicki Centar Nis
Niš
Klinicki Centar Vojvodine
Novi Sad
Germany3 sites
Universitätsklinikum Bonn, Radiologische Universitätsklinik
Bonn
Universitäts GefäßCentrum Uniklinikum Dresden
Dresden
Klinik für Innere Medizin I - Angiologie / Kardiologie
Leipzig
United States2 sites
Kaleida Health System
Buffalo, New York, 14209
Cleveland Clinic
Cleveland, Ohio, 44195
Bulgaria2 sites
Clinic of Vascular Surgery and Angiology
Sofia, 1309
Tokuda Hospital Sofia
Sofia
India2 sites
Life Care Institute of Medical Sciences and Research
Gujarat
Gokula Metropolis Clinical Research Centre, M. S. Ramaiah Hospital
Karnataka
Slovakia2 sites
Oddelenie diagnostickej a intervencnej radiologie, The National Institute of Cardiovascular Diseases
Bratislava, 83348
The Eastern Slovak Institute of Cardiovascular Diseases
Košice
About this study
Official title: A Phase 2, Randomized, Open-label (With Blinded Plasminogen Activator and Placebo Control Groups) Study to Evaluate the Effects of Different Intra-thrombus Infusion Regimens of Plasmin (Human) Compared to Plasminogen Activator and Placebo In Patients With Acute Lower Extremity Native Artery or Bypass Graft Occlusion
The primary purpose of this Phase 2 study is to optimize Plasmin delivery by comparing different delivery regimens in patients with peripheral arterial occlusion. The study includes a blinded plasminogen activator treatment group and a blinded plasminogen activator placebo group. The study will also assess safety and tolerability of Plasmin at 150 and 250 mg doses.
- Conditions
- Acute Peripheral Arterial Occlusion
- Being tested
- Plasmin, Plasminogen Activator, Placebo
- Keywords
- Acute Limb Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlasminBiological
Also called Plasmin (Human)
Plasmin prepared in 0.9% saline for injection
Plasminogen ActivatorBiological
Also called tissue plasminogen activator (tPA), urokinase (UK)
Plasminogen activator used according to the Investigator's clinical judgment.
PlaceboOther
Also called Normal saline
Normal saline for injection at the same volume as the plasminogen activator.
| Study group | Role | What they receive |
|---|---|---|
| Plasmin Open-label Treatment Group A | Experimental | Open-label 150 mg Plasmin administered without initial proximal pulse; 5-hour infusion using 10 mL/hour infusion rate. Receives: Biological: Plasmin |
| Plasmin Open-label Treatment Group B | Experimental | Open-label 150 mg Plasmin administered with initial proximal pulse; 5-hour infusion using 15 mL/hour infusion rate Receives: Biological: Plasmin |
| Plasmin Open-label Treatment Group C | Experimental | Open-label 150 mg Plasmin administered with proximal pulse; 5 hour infusion using 30 mL/hour infusion rate. Receives: Biological: Plasmin |
| Plasmin Open-label Treatment Group D | Experimental | Open-label 150 mg Plasmin administered with proximal pulse; 2-hour infusion using 35 mL/hour infusion rate Receives: Biological: Plasmin |
| Plasminogen Activator Blinded Group E | Active comparator | PA administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice Receives: Biological: Plasminogen Activator |
| PA Placebo Blinded Treatment Arm F | Placebo comparator | PA placebo (normal saline for injection) administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice for PA administration Receives: Other: Placebo |
| Plasmin Open-label Treatment Group G | Experimental | Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 60 mL/hour infusion rate Receives: Biological: Plasmin |
| Plasmin Open-label Treatment Group H | Experimental | Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 75 mL/hour infusion rate Receives: Biological: Plasmin |
| Plasmin Open-label Treatment Group I | Experimental | Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter Receives: Biological: Plasmin |
| Plasmin Open-label Treatment Group J | Experimental | Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 35 mL/hour infusion rate with balloon occlusion catheter Receives: Biological: Plasmin |
| Plasmin Open-label Treatment Group M | Experimental | Open-label 250 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter Receives: Biological: Plasmin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Proportion of Subjects With >50% Thrombolysis
The proportion of subjects with >50% thrombolysis at the end of treatment compared to baseline by arteriography.
Measured: 5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)
Secondary outcomes (1)
The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability.
The incidence of major and minor bleeding events, deaths, adverse events, serious adverse events, and abnormal laboratory values as a measure of safety and tolerability.
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 posted18 Oct 2010 (estimated)
- Study startDec 2010
- Primary completionDec 2015
- Study completionJan 2016
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 (1)Papers the sponsor has linked to this study.
- Other trials for Acute Peripheral Arterial OcclusionStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 174 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grifols Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kecia Courtney, Study director, Grifols Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01222117
- Sponsor's protocol ID
- T05018-2004
- Other IDs
- 2010-019760-36
- Status last verified
- Nov 2016
- First submitted
- 13 Oct 2010
- Last updated
- 16 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Comerota AJ, Davidovic L, Hanna K, Courtney KL, Shlansky-Goldberg RD. Phase 2, randomized, open-label study on catheter-directed thrombolysis with plasmin versus rtPA and placebo in acute peripheral arterial occlusion. J Drug Assess. 2019 Apr 9;8(1):43-54. doi: 10.1080/21556660.2019.1586402. eCollection 2019.
PubMed 31069128
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Open-label (With Blinded Plasminogen Activator and Placebo Control Groups) Study to Evaluate the Effects of Different Intra-thrombus Infusion Regimens of Plasmin (Human) Compared to Plasminogen Activator and Placebo In Patients With Acute Lower Extremity Native Artery or Bypass Graft Occlusion
- ClinicalTrials.gov ID
- NCT01222117
- Acronym / sponsor ID
- T05018-2004
- Conditions
- Acute Peripheral Arterial Occlusion
- Keywords
- Acute Limb Ischemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 174 participants (actual)
- Lead sponsor
- Grifols Therapeutics LLCIndustry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 18 Oct 2010 (estimated)
- Results
- Posted 30 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this Phase 2 study is to optimize Plasmin delivery by comparing different delivery regimens in patients with peripheral arterial occlusion. The study includes a blinded plasminogen activator treatment group and a blinded plasminogen activator placebo group. The study will also assess safety and tolerability of Plasmin at 150 and 250 mg doses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Plasmin Open-label Treatment Group A | Experimental | Biological: PlasminOpen-label 150 mg Plasmin administered without initial proximal pulse; 5-hour infusion using 10 mL/hour infusion rate. |
| Plasmin Open-label Treatment Group B | Experimental | Biological: PlasminOpen-label 150 mg Plasmin administered with initial proximal pulse; 5-hour infusion using 15 mL/hour infusion rate |
| Plasmin Open-label Treatment Group C | Experimental | Biological: PlasminOpen-label 150 mg Plasmin administered with proximal pulse; 5 hour infusion using 30 mL/hour infusion rate. |
| Plasmin Open-label Treatment Group D | Experimental | Biological: PlasminOpen-label 150 mg Plasmin administered with proximal pulse; 2-hour infusion using 35 mL/hour infusion rate |
| Plasminogen Activator Blinded Group E | Active comparator | Biological: Plasminogen ActivatorPA administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice |
| PA Placebo Blinded Treatment Arm F | Placebo comparator | Other: PlaceboPA placebo (normal saline for injection) administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice for PA administration |
| Plasmin Open-label Treatment Group G | Experimental | Biological: PlasminOpen-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 60 mL/hour infusion rate |
| Plasmin Open-label Treatment Group H | Experimental | Biological: PlasminOpen-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 75 mL/hour infusion rate |
| Plasmin Open-label Treatment Group I | Experimental | Biological: PlasminOpen-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter |
| Plasmin Open-label Treatment Group J | Experimental | Biological: PlasminOpen-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 35 mL/hour infusion rate with balloon occlusion catheter |
| Plasmin Open-label Treatment Group M | Experimental | Biological: PlasminOpen-label 250 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Unilateral limb ischemia - Society of Vascular Surgery Categories I and IIa
- Onset of symptoms less than or equal to 14 days
- Thrombosed infrainguinal bypass graft or native artery
- Diagnosis by arteriography of occlusive thrombus in graft or artery
- Ability to embed the infusion catheter into the thrombus
Key exclusion criteria (24 listed)
- Any medical or social condition that may interfere with study participation
- Women who are pregnant or lactating
- Hemorrhagic stroke history
- Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack) within one year
- Intracranial or spinal neurosurgery, or severe intracranial trauma in the last 3 months
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 |
|---|---|---|
| PlasminAlso: Plasmin (Human)Plasmin prepared in 0.9% saline for injection | Biological | Plasmin Open-label Treatment Group A, Plasmin Open-label Treatment Group B, Plasmin Open-label Treatment Group C, Plasmin Open-label Treatment Group D, Plasmin Open-label Treatment Group G, Plasmin Open-label Treatment Group H, Plasmin Open-label Treatment Group I, Plasmin Open-label Treatment Group J, Plasmin Open-label Treatment Group M |
| Plasminogen ActivatorAlso: tissue plasminogen activator (tPA), urokinase (UK)Plasminogen activator used according to the Investigator's clinical judgment. | Biological | Plasminogen Activator Blinded Group E |
| PlaceboAlso: Normal salineNormal saline for injection at the same volume as the plasminogen activator. | Other | PA Placebo Blinded Treatment Arm F |
Primary outcome
The Proportion of Subjects With >50% Thrombolysis
Time frame: 5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)
The proportion of subjects with >50% thrombolysis at the end of treatment compared to baseline by arteriography.
1 secondary outcome
The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability.
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31069128Comerota AJ, Davidovic L, Hanna K, Courtney KL, Shlansky-Goldberg RD. Phase 2, randomized, open-label study on catheter-directed thrombolysis with plasmin versus rtPA and placebo in acute peripheral arterial occlusion. J Drug Assess. 2019 Apr 9;8(1):43-54. doi: 10.1080/21556660.2019.1586402. eCollection 2019.
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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.
Kecia Courtney study director
Grifols Therapeutics
39 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Plasmin and Plasminogen Activator in people with Acute Peripheral Arterial Occlusion, run by Grifols Therapeutics LLC at 39 sites in 12 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 6 inclusion and 24 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 16 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in Poland, Czechia, Belgium, Peru, Romania and 7 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. Some participants in this study may receive a placebo. 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 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?
Yes. Results are posted in the registry (first posted 30 May 2016). 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?
The Proportion of Subjects With >50% Thrombolysis (time frame: 5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)). 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 NCT01222117, which also lists 1 linked publication.
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 16 Jan 2017.