CTRI/2011/04/001657 [Registered on: 01/04/2011] Trial Registered Prospectively
Last Modified On:
16/06/2011
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug Biological
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
A clinical trial to compare different administrations of the investigational drug Plasmin in patients with a clot in an artery of the lower leg.
Scientific Title of Study
T05018-2004: 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 Grafi Occlusion
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NCT01222117
ClinicalTrials.gov
TO5018-2004
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Ataali shaikh
Designation
General Manager
Affiliation
Kendle India
Address
General Manager Kendle India Pvt Ltd. Unit 002, Ground Floor, Tower C, Cyber Park, Sector 39, Gurgaon HARYANA 122001 India
Phone
911244536357
Fax
911244536301
Email
shaikh.ataali@kendle.com
Details of Contact Person Scientific Query
Name
Vishal Patel
Designation
Senior Project Leader
Affiliation
Kendle India
Address
Senior Project Leader Global Project Management
Kendle,
B-901, Safal Pegasus, 100 Feet Road,
Near Auda Garden, Prahladnagar,
Anand nagar Road.
Ahmedabad - 380 051
Gujarat, INDIA. Ahmadabad GUJARAT 380 051 India
Phone
917940213610
Fax
917940213601
Email
patel.vishal@kendle.com
Details of Contact Person Public Query
Name
Vivek Malhotra
Designation
Regulatory Manager
Affiliation
Kendle India
Address
Regulatory Manager Kendle India Pvt Ltd. Unit 002, Ground Floor, Tower C, Cyber Park, Sector 39, Gurgaon HARYANA 122001 India
Phone
911244536357
Fax
911244536301
Email
malhotra.vivek@kendle.com
Source of Monetary or Material Support
Talecris Biotherapeutics, Inc.4 10 1 Research Commons, 79 T. W. Alexander Drive, Research Triangle Park, North Carolina 27709 USA
Primary Sponsor
Name
Talecris Biotherapeutics Inc
Address
4101 Research Commons, 79 T. W. Alexander Drive, Research Triangle Park, North Carolina 27709 USA
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Kendle India Private Limited
Kendle India Pvt Ltd.
Unit 002, Ground Floor,
Tower C, Cyber Park, Sector 39,
Gurgaon 122001
Haryana, India
Tel 911244536 300
Countries of Recruitment
India Sri Lanka Belgium Brazil Bulgaria Czech Republic Germany Peru Poland Romania Russian Federation Serbia Slovakia Spain Ukraine United States of America
Sites of Study
No of Sites = 16
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Kamal Sharma
Apollo Hospitals International Limited, Department of Cardiology,
Clinical Research Department Second Floor Plot No. 1 A, Bhat GIDC Estate, Gandhinagar-382428, Gujarat, India. Ahmadabad GUJARAT
09925195662
kamalsharma1975@rediffmail.com
Dr Tarun Gandhi
CHL Apollo Hospitals, Department of Cardio thoracic and Vascular Surgery.
Clinical Research Department
Second Floor
A.B. Road, Near L.I.G. Triangle, Indore-452008, Madhya Pradesh, India 452008 Indore MADHYA PRADESH
9009090203
doc_tgandhi@yahoo.co.in
Dr S Sudindran
Department of Vascular surgery, Amrita Institute of medical science & Research,
1st Floor, Tower 1, Kochi, Kerala, 682041 Thiruvananthapuram KERALA
9995022194
sudhi@aims.amrita.edu
Dr Hemanth Pandharpurkar
Dept. of Surgery, St. Johns Medical College Hospital
Amrita institute of Medical sciences Dr. Sudhindran Institutional Ethics Committee, Amrita Institute of Medical Sciences and research Center
Submittted/Under Review
Apollo Hospitals International Limited Dr. Kamal Sharma Ethics Committee - Apollo Hospitals International Limited
Approved
CHL-Apollo Hospital Dr. Tarun Gandhi CHL ? Apollo Hospitals - Ethics Committee
Approved
Hospital Ethics Committee, Life care Institute of Medical science and Research, Dr. Sameer Dani
Approved
Indraprastha Appolo Hospital Dr. Rakesh mahajan Ethics Committee on Clinical Trials, Indraprastha Apollo Hospitals
Submittted/Under Review
M.S. Ramaiah Memorial Hospital Dr. Sanjay Desai M.S. Ramaiah Medical College and Teaching Hospital, Ethical review Board.
Approved
Max Devki devi Dr. Kumud Rai Institutional Review Board
Submittted/Under Review
Medanta, The medicity Dr. Rajiv Parakh Medanta Instituional Review Board and Medanta Institutinal ethics committee.
Submittted/Under Review
Nizam Institute of Medical sciences Dr. R.K. Pinjala Institutional Ethics Committee, Nizam?s Institute of Medical Sciences
Approved
Omega Hospital Dr. Mukunda Kumbla Canara Research Ethical Committee
Approved
Ruby Hal Clinic Dr. Dhanesh Kamerkar Ethics Committee-Poona Medical Research Foundation,
Approved
Shalby Hospital Dr. Sunil Thanvi Ethics Committee Shalby Hospitals
Approved
Sir Ganga Ram Hospital Dr. Ashwani Mehta Ethics Committee Sir Gangaram Hospital,
Submittted/Under Review
Sree Chitra Tirunal Institute for Medical Sciences & Technology Dr. Arun Gupta Ethics Committee, Sree Chitra Tirunal Institute for Medical Sciences & Technology
Submittted/Under Review
St. John Medical college Dr. Hemanth Pandharpurkar Ethical Review Board
Approved
Sterling Hospital Dr. Shrenik Shah Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Patients With Acute Lower Extremity Native Artery or
Bypass Grafi Occlusion,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo (0.9% NaCl for injection)
Volume to match the equivalent PA volume according to investigator clinical judgment.
Intervention
Plasmin (Human)
150 mg Plasmin - Distal Pulse and Infusion
Intervention
Plasmin (Human)
150 mg Plasmin - Proximal Pulse and 2-Hr High Infusion Rate
Intervention
Plasmin (Human)
150 mg Plasmin - Proximal Pulse and High Infusion Rate
Intervention
Plasmin (Human)
150 mg Plasmin - Proximal Pulse and Infusion
Comparator Agent
Plasminogen Activater
PA Dose And Volume According To The Investigators Clinical Judgment
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Inclusion Criteria
1. Unilateral limb ischemia: symptomatic, SVS acute ischemic Categories I and IIa
2. Onset of symptoms less than or equal to 14 days
3. Thrombosed (non-embolic) infrainguinal graft (synthetic, autologous, or single
outflow composite) or infrainguinal native artery. For native arteries, occlusions
of greater than or equal to 10 cm in length are eligible.
4. Diagnosis of occlusive thrombus in the graft or artery by arteriography after informed consent is obtained
5. Ability to access the thrombus with the infusion catheter and successfully embed
the infusion segment of the infusion catheter.
6. Subject must be able to give written informed consent prior to study entry
7. Age greater than or equal to 18 years
8. Women of child bearing potential must use adequate contraception for the duration
of the study and must have a negative pregnancy test prior to study entry
(Since there is no upper age limit defined for this trial for the CTRI registration purpose we have included the upper age limit to be considered as 99 years).
ExclusionCriteria
Details
Exclusion Criteria
General
1. Any medical or social condition that may interfere with the subject successfully completing the study
2. Women who are pregnant or lactating, or first 10 days post-partum
Past Medical History
3. Cardiopulmonary resuscitation in the last year
4. Previous systemic or anaphylactoid allergy to contrast agent, streptokinase, or blood products (subjects allergic to shellfish or iodine are permitted to enter the study).
Contraindications To Thrombolysis
5. Ineligible for thrombolytic treatment for any reason. Specific exclusions include:
a. History of hemorrhagic stroke
b. Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack [TIA]) within the past year
c. Intracranial or spinal neuro-surgery or severe intracranial trauma in the past 3 months
d. Major surgery, organ biopsy, or major trauma within the past 10 days
e. Lumbar puncture or non-compressible arterial puncture in the past 10 days
f. Intra-ocular surgery within the past 10 days
g. Active gastrointestinal or organ bleeding. Minor bleeding such as normal menses, cystitis, or minor hemorrhoidal bleeding are not exclusions
h. Uncontrolled arterial hypertension, defined as a systolic blood pressure >180 millimeters of mercury (mmHg) or diastolic blood pressure >110 mmHg. Thesubject will be eligible if the hypertension is controlled at the time of study enrollment.
i. Known intracranial neoplasm, aneurysm, or arterio-venous malformation
j. Current bleeding diathesis
k. Platelet count <75 x 109/L Current Medical Status
6. Active graft infection
7. Occlusion occurred within one month of synthetic graft placement
8. Occlusion occurred within 6 months of autologous graft placement
9. A sequential composite graft with dual outflows to correct multiple occlusions
10. Deemed by the Investigator to be medically unable to tolerate open vascular procedure
11. Known prothrombotic state, e.g., anti-cardiolipin antibody, human immunodeficiency virus (HIV)-associated peripheral vascular disease
12. Known contraindication to heparin (e.g., history of heparin-induced thrombocytopenia)
13. Hemoglobin <10.0 g/dL (low hemoglobin at screening in the absence of active bleeding may be corrected by transfusion). Hemoglobin testing can be repeated.
14. Impaired renal function or renal disease that constitutes a contraindication to contrast arteriography, including a screen/baseline creatinine of >2.0 mg/dL. Creatinine may be repeated following hydration for prerenal azotemia.
Prior/Concurrent Therapy
15. Previous treatment with Plasmin
16. Treatment with full dose plasminogen activator (e.g., streptokinase (e.g., Streptase®, Kabikinase®), anistreplase (Eminase®), alteplase (e.g., Activase®), reteplase (e.g., Retavase®), tenecteplase (TNKase?), urokinase (UK, [Abbokinase®]) within the last 48 hours
17. Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within 5 days prior to study entry or at any time during the study, e.g., abciximab (ReoPro®),eptifibatide (Integrilin®) or tirofiban (Aggrastat®)
18. Treatment with oral anticoagulants (e.g., warfarin, acenocumarol), and with an international normalized ratio (INR) of >1.7 (elevated INR at screening may be corrected prior to study enrollment). INR testing can be repeated.
Others
19. Participation in another clinical study within 30 days prior to entry (imaging studies without investigative treatment are permitted), or concomitant participation in another study.
20. Mentally challenged adult subjects who cannot give independent written informed consent.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
On-site computer system
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
The proportion of subjects with 50% thrombolysis at the end of treatment compared to baseline by arteriography.
5 hr timepoint
Secondary Outcome
Outcome
TimePoints
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.
DAY 30
Target Sample Size
Total Sample Size="100" Sample Size from India="20" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a Phase 2, multi-center, multi-national, randomized, open-label study (with blinded PA and PA Placebo groups) of Plasmin in subjects with acute angiographically confirmed lower extremity native artery or bypass graft occlusion. Subjects will be enrolled into one of six parallel treatment groups: four Plasmin Treatment groups differing only in administration technique and two blinded groups (a Blinded PA Treatment Group and a Blinded PA Placebo Group). The administration regimens for the Plasmin groups have been designed to examine the effect of different infusion catheter positions, different Plasmin pulse regimens, and different rates of Plasmin continuous infusion/volume on the thrombolytic activity and safety of Plasmin treatment. Acute lower extremity ischemia will be diagnosed by a PAO assessment examination for the purpose of classifying the subject into the Society for Vascular Surgery (SVS) acute limb ischemia category. This includes findings of sensory loss,muscle weakness, and presence or absence of arterial and venous Doppler signals (Doppler is optional at screening and baseline). Ischemic signs and symptoms of pain, paresthesias, paralysis, poikilothermia, pallor, and pulselessness will be documented. Approximately 100 subjects, ages of 18 or greater, are planned to be randomized in a 2:2:2:2:1:1 ratio to four Plasmin treatment groups (Groups A, B, C, and D, 20 subjects/group), one Blinded PA Treatment Group (Group E, 10 subjects/group), and one Blinded PA Placebo Group (Group F, 10 subjects/group) at investigative sites in multiple countries. Approximately eighty (80) subjects will be dosed with Plasmin, approximately ten (10) subjects will be dosed with PA and approximately ten (10) subjects will be dosed with PA Placebo. Subjects will be stratified at randomization into each treatment group by occluded lower extremity blood vessel type (native artery or graft) to ensure approximate equal balance of each presenting vessel type across treatment groups. Globally following countries are involved in this clinical trial: India, Sri Lanka, Belgium, Bulgaria, Czech Republic, Germany, Poland, Romania, Russia, Serbia, Slovakia, Spain, Ukraine, Brazil and Peru.