Safety and Efficacy of Tissue Plasminogen Activator (tPA) in Neonates and Infants

Sponsor

University of Louisville (Other)

Overall Status

Terminated

CT.gov ID

NCT00265005

Collaborator

Genentech, Inc. (Industry)

Enrollment

Location

Arm

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if alteplase is effective in dissolving a clot in a catheter in a large vein (central venous line or PICC line) or artery in infants less than 6 months of age.

Condition or Disease	Intervention/Treatment	Phase
Thrombosis	Drug: alteplase	Phase 1

Detailed Description

Hospitalized patients with central access devices will be screened. Ninety subjects with at least one occluded lumen of a central access device will be eligible. Thirty subjects will be enrolled in each of the following age groups: 28-<34 weeks CGA, 34- < 40 weeks CGA, and 40 weeks to 66 weeks CGA.

Inclusion Criteria

Subjects will be eligible if the following criteria are met:

Ability to provide written informed consent by the parent or legal guardian and comply with study assessments for the full duration of the study.
Hospitalized premature neonates (28-< 34 weeks CGA), term neonates (34-<40 weeks CGA) and infants (40 weeks to 66 weeks CGA).
Presence of a central access device. All types of permanent and temporary catheters are eligible [e.g., central venous catheter (CVC), peripherally-inserted central catheter (PICC), umbilical arterial catheter (UAC), or umbilical venous catheter (UVC)] except hemodialysis catheters. The catheter must be properly inserted as evidenced by the ability to have used the catheter at least once for its intended purpose (i.e., to withdraw blood and/or infuse fluids) and documentation of correct catheter placement radiographically within 48 hours of the catheter becoming non-patent.
partial or total occlusion of at least one lumen of the catheter.

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from this study:

CGA > 66 weeks
Incorrect catheter placement (see section 3.1) or evidence of mechanical occlusion
By clinical examination there is evidence that the catheter has migrated or become dislodged. This is determined by confirming the depth to which the catheter had been positioned on insertion or adjusted to after placement.
There is evidence of mechanical obstruction of the catheter on the portion (is any) that is visible from the catheter hub to the skin insertion site (e.g., kinking or twisting of the catheter).
Occlusion due to suspected drug precipitate in the opinion of the investigator
Active internal bleeding, involving intracranial and retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts
Recent history (i.e., < 6 months) of intraventricular hemorrhage (IVH) or other active intracranial process that could predispose to intracranial bleeding
Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention
Any of the following known or suspected hemorrhagic events within the preceding 7 days or any other significant bleeding risk:
Gastrointestinal bleeding
Intra-ocular surgery
Any of the following known events or suspected hemorrhagic events within the preceding 48 hours
Major surgery (excluding central line placement)
Organ biopsy
Major trauma
Puncture of a non-compressible vessel within the previous 48 hours
Treatment with indomethacin within the previous 48 hours
Received any fibrinolytic agent within 24 hours of enrollment
Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis
Known hypersensitivity to Alteplase or any component in the formulation of CathfloTM Activase®
Prior enrollment in the current study
Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or the patient has a known condition for which bleeding constitutes a significant hazard
Participation in another interventional investigation or trial within the previous 30 days
Documented or suspected catheter infection
Thrombocytopenia (i.e. platelet count < 20,000)

METHOD OF TREATMENT ASSIGNMENT This is an open-label study and all subjects will receive CathfloTM Activase.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dose-Ranging, Safety And Efficacy Of Cathflo(TM) Activase(R) (Alteplase) For The Treatment Of Central Catheter Occlusion In Neonates And Infants; Phase I

Study Start Date :

Jun 1, 2005

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All All subjects receive active drug up to a total of 3 doses	Drug: alteplase Iv administration of 1 mg/ml up to two times and 2 mg/ml if needed. Other Names: Cathflo Activase

Arm

Intervention/Treatment

Experimental: All

All subjects receive active drug up to a total of 3 doses

Drug: alteplase

Iv administration of 1 mg/ml up to two times and 2 mg/ml if needed.

Other Names:

Cathflo Activase

Outcome Measures

Primary Outcome Measures

Restoration of central access device patency following one, two or three instillations of t-PA. [within 180 minutes of administering the study drug]

Secondary Outcome Measures

Restoration of patency following instillation of 1 mg/mL (i.e., first instillation) [within 60 minutes from the first instillation of study drug]
Restoration of patency following instillation of 1 mg/mL (i.e., second instillation) [within 60 minutes from the second instillation of study drug]
Restoration of patency following instillation of 2 mg/mL (i.e., third instillation) [within 60 minutes from the third instillation of study drug]
The following safety outcome measure will be evaluated: • Major bleeding complications • Sepsis • Embolic events • All serious adverse events [Within 14 days of study drug administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

28 Weeks to 66 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability to provide written informed consent by the parent or legal guardian and comply with study assessments for the full duration of the study
Hospitalized premature neonates (28- < 34 weeks CGA), term neonates (34 weeks-< 40 weeks CGA) and infants (> = 40 weeks to 6 months CGA).
Presence of central access device. All types of permanent and temporary catheters are eligible [e.g., central venous catheter (CVC), peripherally-inserted central catheter (PICC), umbilical arterial catheter (UAC), or umbilical venous catheter (UVC)] except hemodialysis catheters. The catheter must be properly inserted as evidenced by the ability to have used the catheter at least once for its intended purpose (i.e., to withdraw blood and/or infuse fluids)and documentation correct catheter placement radiographically within 48 hours of the catheter becoming non-patent.
Partial or total occlusion of at least one lumen of the catheter

Exclusion Criteria:

CGA > 66 weeks
Incorrect catheter placement or evidence of mechanical occlusion
Occlusion due to suspected drug precipitate
Active internal bleeding, involving intracranial or retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts
Recent history (i.e., < 6 months) of intraventricular hemorrhage (IVH) or other active intracranial process that could predispose to intracranial bleeding
Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention
Any of the following known or suspected hemorrhagic events within the preceding 7 days or any other significant bleeding risk:
Gastrointestinal bleeding
Intra-ocular surgery
Any of the following known events or suspected hemorrhagic events within the preceding 48 hours
Major surgery (excluding central line placement)
Organ biopsy
Major trauma
Puncture of a non-compressible vessel within the previous 48 hours
Treatment with indomethacin within the previous 48 hours
Received any fibrinolytic agent within 24 hours of enrollment
Known risk for embolization, including history of left heart thrombus, mitral mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis
Known hypersensitivity to alteplase or any component in the formulation of CathfloTM Activase®
Prior enrollment in the current study
Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or the patient has a known condition for which bleeding constitutes a significant hazard
Participation in another simultaneous interventional medical investigation or trial
Documented or suspected catheter infection
Thrombocytopenia (i.e. platelet count < 20,000)