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

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

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.

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.

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)