ARTSS-2: A pilot, phase IIb, randomised, multicentre, safety and activity trial of Argatroban in combination with TPA (Alteplase) Stroke Study
| ISRCTN | ISRCTN51505768 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN51505768 |
| Secondary identifying numbers | 13646 |
- Submission date
- 18/01/2013
- Registration date
- 23/01/2013
- Last edited
- 20/01/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Mrs Claire Macdonald
Scientific
Scientific
Newcastle Clinical Trials Unit
Institute of Health and Society
4th Floor William Leech Building
Framlington Place
Newcastle Upon Tyne
NE2 4HH
United Kingdom
| claire.macdonald@newcastle.ac.uk |
Study information
| Study design | Pilot phase IIb randomised multicentre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | ARTSS-2: A pilot, phase IIb, randomised, multi-center trial of Argatroban in combination with recombinant tissue plasminogen activator for acute stroke |
| Study acronym | ARTSS-2 |
| Study objectives | A pilot, phase IIb, randomised, multicentre trial of Argatroban in combination with recombinant tissue plasminogen activator for acute stroke. Recombinant tissue plasminogen activator (rtPA), the only proven treatment for acute ischemic stroke, fails to reperfuse the brain in most patients with large thrombi. In a Phase IIa low dose safety study (n=65), conducted by University of Texas Houston, delivering Argatroban with rtPA indicated that both drugs appear safe when delivered concomitantly and recanalisation rates were greater than with historical controls. The purpose of the trial is to estimate the overall treatment benefit (improvement in disability) among stroke patients treated with rtPA (Alteplase) who are randomised to receive either lowdose Argatroban, highdose Argatroban or neither. This study will provide evidence based hypotheses and data needed to design a larger definitive trial. The study will be conducted in six hospitals across the UK and will recruit males and females over 18 years of age with acute ischemic stroke. |
| Ethics approval(s) | NRES Committee North West Greater Manchester South, 24/07/2012, ref:12/NW/0425 |
| Health condition(s) or problem(s) studied | Stroke |
| Intervention | Three treatment arms (n=35 each) will be enrolled: 1. Low-dose Argatroban* (1.0µg/kg/min continuous infusion of Argatroban, preceded by a 100 µg/kg bolus administered over 3-5 minutes Infusion will be titrated to achieve an aPTT of 1.75 times baseline - not to exceed 10 µg/kg/min) + usual care IV-rt-PA; 2. High-dose Argatroban* 3.0 µg/kg/min continuous infusion of Argatroban, preceded by a 100 µg/kg bolus administered over 3-5 minutes Infusion will be titrated to achieve an aPTT of 2.25 times baseline - not to exceed 10 µg/kg/min) + usual care IV-rt-PA; 3. Intravenous-rt-PA alone (usual care). *Argatroban infusions will continue for a maximum of 48 hours. During the course of the treatment, patients will be evaluated via Computed Tomography (CT) angiogram, CT scans, vital signs, laboratory measurements, and neurological and unctional outcomes. Patients will also be evaluated at 24 hours following the onset of the stroke, Day 7 or discharge (whichever comes first) and at day 90. Sponsor's EEA representative: The Newcastle upon Tyne Hospitals NHS Foundation Trust Freeman Hospital Freeman Road High Heaton Newcastle upon Tyne NE7 7DN email: Trust.R&D@nuth.nhs.uk |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Argatroban |
| Primary outcome measure | Excellent functional outcome as measured by the percentage of patients with a 0 or 1 on the modified Rankin Scale (mRS) at day 90 as assessed by study personnel blinded to treatment |
| Secondary outcome measures | 1. Safety as measured by the incidence of: 1.1. Symptomatic intracranial haemorrhage (sICH) 1.2. Parenchymal Haemorrhage 2 (PH-2) 1.3. Major systemic haemorrhage. 2. Rates and completeness of arterial recanalisation assessed at baseline and 2-3 hours by CT-Angiogram (CTA) 3. Neurological deficits improvement from baseline to 2 hours, 24 hours, end of Argatroban infusion, Day 7/discharge and day 90 as measured by NIHSS 4. Quality of Life obtained by standard gamble, time-trade-off method and visual analogue scale (VAS) 5. Cost and cost-effectiveness analysis 5.1 Medical costs associated with each treatment 5.2 Incremental cost-effectiveness ratio (change in cost divided by quality of life gained) |
| Overall study start date | 01/03/2013 |
| Completion date | 31/07/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | UK Sample Size: 50 |
| Key inclusion criteria | 1. Disabling ischemic stroke symptoms with onset < 3 hours treated with IV rtPA (alteplase) by local standards*. * or <= 4.5 hours according to local standard of care 2. Age >= 18 3. National Institutes of Health Stroke Scale (NIHSS) >= 10* or any NIHSS with an intracranial clot should be demonstrated on neurovascular imaging (TCD or CTA) in any one of the following areas: distal ICA, MCA (M1 or M2), PCA (P1 or P2), distal vertebral or basilar artery 3.1. TCD criteria: TIBI 0, 1, 2 or 3 3.2. CTAngiogram: TIMI 0 or 1 * NIHSS = 10, demonstration of clot on neuroimaging is not necessary (i.e., enrollment can proceed with noncontrast head CT alone), but if performed, a clot must be demonstrated 4. For those patients who will undergo repeat CT Angiogram at 23 hours, estimated glomerular filtration rate (eGFR) must be >= 60 mL/min/1.73m2 5. Females of childbearing potential must have a negative serum pregnancy test prior to the administration of trial medication 6. Signed (written) informed consent by the patient or the patients legal representative and/or guardian |
| Key exclusion criteria | 1. Patients whom the treating physician is planning (or could plan) to treat with intraarterial thrombolysis or other endovascular procedures (i.e., mechanical clot retrieval) aimed at recanalisation 2. Evidence of intracranial haemorrhage (ICH) on baseline CT scan or diagnosis of a nonvascular cause of neurologic deficit 3. NIHSS Level of Consciousness score (1a) >= 2 4. Preexisting disability with mRS >= 2 5. CT scan findings of hypoattenuation of the xray signal (hypodensity) involving >= 1/3 of the MCA territory 6. Any evidence of clinically significant bleeding, or known coagulopathy 7. INR >1.5 8. Patients with an elevated activated partial thromboplastin time (aPTT) greater than the upper limit of normal 9. Patients currently, or within the previous 24 hours, on an oral direct thrombin inhibitor 10. Heparin flush required for an IV line. Line flushes with saline only. 11. Any history of intracranial haemorrhage, known arteriovenous malformation or unsecured cerebral aneurysms 12. Significant bleeding episode within the 3 weeks before study enrollment 13. Major surgery or serious trauma in last 2 weeks 14. Patients who have had an arterial puncture at a noncompressible site, biopsy of parenchymal organ, or lumbar puncture within the last 2 weeks 15. Previous stroke, myocardial infarction (MI), post myocardial infarction pericarditis, intracranial surgery, or significant head trauma within 3 months 16. Uncontrolled hypertension (SBP > 185 mmHg or DBP >110 mmHg) that does not respond to intravenous antihypertensive agents 17. Surgical intervention (any reason) anticipated within the next 48 hours 18. Known history of clinically significant hepatic dysfunction or liver disease including a current history of alcohol abuse 19. Abnormal blood glucose <50 mg/dL (2.7 mmol/L) 20. History of primary or metastatic brain tumor 21. Current platelet count < 100,000/mm3 22. Life expectancy < 3 months 23.Patients who, in the judgment of the investigator, needs to be on concomitant (i.e., during the Argatroban infusion) anticoagulants other than Argatroban, including any form of heparin, unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), defibrinogenating agent, dextran, other direct thrombin inhibitors or thrombolytic agents, GPIIb/IIIa inhibitor or warfarin. [*Caveat: However, if in the judgment of the investigator a patient needs to be anticoagulated, but this can be deferred for 48 hours, then they could be included.] 24. Currently participating or has participated in any investigational drug or device study within 30 days before the first dose of study medication 25. Known hypersensitivity to Argatroban or its agents 26. Additional exclusion criteria if patient presents between 34.5 hours: 26.1. Age >80 26.2. Currently taking oral anticoagulants (regardless of INR) 26.3. A history of stroke and diabetes. 26.4. NIHSS > 25 |
| Date of first enrolment | 01/03/2013 |
| Date of final enrolment | 31/07/2014 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Newcastle Clinical Trials Unit
Newcastle Upon Tyne
NE2 4HH
United Kingdom
NE2 4HH
United Kingdom
Sponsor information
The University of Texas Health Science Center at Houston (USA)
University/education
University/education
7000 Fannin, Suite 1200
Houston
Texas
77030
United States of America
| Website | http://www.uthouston.edu/ |
|---|---|
"ROR" |
https://ror.org/03gds6c39 |
Funders
Funder type
Government
National Institutes of Health (USA)
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Institutos Nacionales de la Salud, US National Institutes of Health, NIH
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/09/2015 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
20/01/2020: Internal review.
13/02/2017: Publication reference added.
10/04/2014: The overall trial end date was changed from 30/04/2014 to 31/07/2014.
