Dysfunctional Hemodialysis CathetersPhase 3TROPICS 4NCT00396253

A Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis (HD) Catheters

A Phase 3 study testing Tenecteplase in people with Dysfunctional Hemodialysis Catheters, run by Genentech, Inc..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This was a Phase III, open-label study conducted at 44 centers in the United States, Canada, and Puerto Rico. 223 subjects who required hemodialysis (HD) and had a dysfunctional HD catheter were enrolled in the study. Read more about this study

Who is it for?: Any age
Conditions the study is for: Dysfunctional Hemodialysis Catheters
What is being tested?: Tenecteplase
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 223 participants
Where: No sites listed yet
Study dates: Nov 2006to Oct 2008
Phase: Phase 3
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 Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Clinically stable, in the opinion of the investigator
Use of a cuffed, tunneled HD catheter
HD prescribed at a blood flow rate (BFR) of ≥300 mL/min
Baseline BFR (at any time during the first 60 minutes of HD) of <300 mL/min at an associated pre-pump negative arterial pressure in the range between and including -240 mmHg and -280 mmHg
Baseline BFR (at any time during the first 60 minutes of HD) at least 25 mL/min below the prescribed BFR
Demonstrated BFR of ≥300 mL/min (using catheter lines in the customary direction) at an arterial pressure in the range of 0 to -280 mmHg in at least one HD session in the 14 days prior to Visit 1
Anticipated use of the same catheter for at least four consecutive HD sessions, on the same type and model of HD apparatus
Able to have fluids infused at the volume necessary to instill study drug into the HD catheter

Who cannot join

HD catheter with sustainable BFR of ≥300 mL/min following subject repositioning
HD catheter inserted <2 days prior to screening
Evidence of a mechanical, non-thrombotic cause of HD catheter dysfunction (e.g., kink in the catheter or suture constricting the catheter) or dysfunction caused by known fibrin sheath
Use of an implantable port
HD catheter that is internally coated with any therapeutic agent (e.g., the Decathlon™ Gold catheter)
Anticipated use of catheter for any other type of diagnostic or therapeutic procedure (i.e., other than HD) during study drug treatment

Show all 20Show fewer

Previously treated in this study or any tenecteplase catheter clearance trial
Use of any investigational drug or therapy (defined as any drug or therapy that is not FDA approved) within 28 days prior to screening
Use of a fibrinolytic agent (e.g. alteplase, tenecteplase, reteplase, or urokinase) within 7 days prior to Visit 1
Known to be pregnant or breastfeeding at screening or at Visit 1
Known bacteremia or known or suspected infection in the HD catheter
Known history of any of the following: intracranial hemorrhage (within the previous 3 years), intracranial aneurysm, or arteriovenous malformation
Use of heparin (unfractionated or low molecular weight) or other anticoagulants (e.g., for the treatment of heparin-induced thrombocytopenia) within 24 hours prior to Visit 1, except for heparin used only during HD or for prophylaxis (e.g., heparin lock or deep vein thrombosis prophylaxis)
Subjects treated with warfarin only: international normalized ratio (INR) >3.0 within 7 days prior to Visit 1, or a target INR range that allows for an INR >3.0
Initiation of or increase in dose of Plavix® (clopidogrel bisulfate) within 7 days prior to Visit 1
Hemoglobin ≥12.0 g/dL if on an erythropoiesis-stimulating agent (e.g., darbepoetin or erythropoietin) and the dose of the erythropoiesis-stimulating agent has not been held or reduced per institutional policy
At high risk for bleeding events or embolic complications (i.e., recent pulmonary embolus, deep vein thrombosis, endarterectomy, or clinically significant right-to-left shunt) in the opinion of the investigator, or with known condition for which bleeding constitutes a significant hazard
BFR of <300 mL/min because of symptomatic hypotension
Uncontrolled hypertension in the opinion of the investigator
Known hypersensitivity to tenecteplase or any component of the formulation

About this study

Official title: A Phase III, Open-Label Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis (HD) Catheters

Read the detailed description

The study consisted of four visits that corresponded to consecutive HD sessions for each patient, as well as one follow-up visit. Patients could receive up to three treatments with open-label tenecteplase during the study: one or two treatments during an initial treatment course, and eligible patients whose catheter became dysfunctional again within 21 days of the first visit received an additional treatment as part of a retreatment (RT) course.

At Visit 1, patients eligible at the beginning of HD had 2 mL (2 mg) of tenecteplase instilled into each of the two lumens of the HD catheter. After a dwell time of 1 hour, study drug was withdrawn and all subjects underwent HD. The duration of the HD session was not fixed by the study protocol, but rather by the site's HD practice, physician orders, and individual patient response during the session. Patients who did not experience treatment success at the end of Visit 1 had 2 mL (2 mg) of tenecteplase instilled into each lumen of their catheter as part of the initial treatment course. The treatment was left to dwell for an extended time, until the second HD session at Visit 2 (up to 72 hours later). Patients who received extended-dwell tenecteplase had the treatment withdrawn from their catheter at the beginning of Visit 2. Patients underwent HD as prescribed or to the extent possible.

Patients who had treatment success at Visit 1 or Visit 2 and had a recurrence of catheter dysfunction within 21 days of Visit 1 and met the re-treatment eligibility criteria had 2 mL (2 mg) of tenecteplase instilled into each lumen, followed by a 1-hour dwell time at re-treatment Visit 1.

Conditions: Dysfunctional Hemodialysis Catheters
Being tested: Tenecteplase
Keywords: HD, TNKase, Hemodialysis, Catheter clearance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TenecteplaseDrug
2 mL (2 mg) of reconstituted lyophilized tenecteplase instilled into each lumen of the HD catheter.

Study groups in NCT00396253
Study group	Role	What they receive
Tenecteplase	Experimental	At each treatment, subjects had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Subjects could receive up to three treatments with tenecteplase, the first two as part of the initial treatment course and one additional treatment as part of the retreatment (RT) course. The first treatment, followed by a 1-hour dwell time, was given to all subjects at Visit 1. At the end of hemodialysis at Visit 1, eligible subjects had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours). Receives: Drug: Tenecteplase

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Who Had Treatment Success With Respect to Blood Flow Rate (BFR) at Visit 1
Treatment success is defined as Blood Flow Rate (BFR) ≥ 300 mL/min and an increase of ≥ 25 mL/min from baseline BFR (without reversal of lines), at an associated arterial pressure in the range of 0 to -280 mmHg, 30 (± 10) minutes prior to the end of hemodialysis and at the end of hemodialysis.
Measured: Visit 1 (the first hemodialysis session in which treatment was administered). BFR was measured at the beginning of hemodialysis (Baseline measurement) and at 30 minutes prior to the end of hemodialysis and at the end of hemodialysis.
Targeted Adverse Events From the Initial Study Drug Administration Through the Start of Visit 2 or Until Instillation of Extended-Dwell Tenecteplase
The primary outcome measure was the number of targeted adverse events, occurring from initial study drug administration through the end of Visit 1 (prior to administration of open-label, extended-dwell tenecteplase) or, for subjects who did not receive open-label, extended-dwell tenecteplase, from initial study administration through the start of Visit 2. Targeted adverse events were defined as intracranial hemorrhage, major bleeding and embolic events, thrombosis, Catheter-related blood stream infection (CRBSIs), and catheter-related complications.
Measured: From initial study drug administration to the end of Visit 1 (prior to administration of open-label, extended-dwell tenecteplase) or, for patients who did not receive extended-dwell tenecteplase, from initial study administration to the start of Visit 2.

Secondary outcomes (7)

Percentage of Participants Who Maintained Catheter Function at Visits 2 and 3
For patients with treatment success at Visit 1 or Visit 2, maintenance of catheter function at subsequent visits was defined as a BFR ≥ 300 mL/min and an increase of ≥ 25 mL/min from baseline BFR (without reversal of lines), at an associated target arterial pressure in the range of 0 to -280 mmHg at the beginning of that HD session (within the first 30 minutes).
Measured: Maintenance BFR measurements were taken at the beginning of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1) and Visit 3 (3rd consecutive HD session, within 72 hours of Visit 2).
Percentage of Participants With Urea Reduction Ratio ≥ 65% at Visit 1
The urea reduction ratio (URR) was calculated from measurements of blood urea nitrogen (BUN) as follows:
(Pre-treatment BUN) - (Post-HD BUN) * 100% / (Pre-treatment BUN)
Pre-treatment URR was assessed within 30-60 minutes after the initiation of HD and does not represent a true baseline value.
Measured: At Visit 1 (first hemodialysis session in which treatment was administered) samples for blood urea nitrogen measurements were taken at the beginning of HD (prior to treatment administration) and after HD was completed.
Percentage of Participants With Urea Reduction Ratio ≥ 65% at Visit 2
The urea reduction ratio (URR) at Visit 2 was calculated for those participants who did not receive extended-dwell tenecteplase at Visit 1 from measurements of blood urea nitrogen (BUN) as follows:
(Pre-HD BUN) - (Post-HD BUN) * 100% / (Pre-HD BUN)
Measured: At Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1) samples for blood urea nitrogen measurements were taken prior to HD and after HD was completed.
Change in Blood Flow Rate From Baseline to the End of Hemodialysis at Visit 1
Change in Blood flow rate (BFR) is the BFR at the end of HD for Visit 1 - BFR at Baseline.
Measured: Baseline (beginning of HD at Visit 1) to the end of HD at Visit 1.
Percentage of Participants Who Failed Treatment at Visit 1 With Treatment Success at Visit 2
Patients who failed treatment at Visit 1 and were treated with extended-dwell tenecteplase were analyzed for Treatment Success at Visit 2. Treatment success at Visit 2 was defined as a BFR ≥ 300 mL/min, without line reversal, and increase of ≥ 25 mL/min from baseline BFR, at an associated target arterial pressure in the range of 0 to -280 mmHg, 30 (± 10) minutes prior to the end of HD and at the end of HD.
Measured: BFR was measured 30 minutes before the end of HD and at the end of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1). Baseline BFR was measured at the beginning of HD at Visit 1.
Percentage of Participants Who Failed Treatment at Visit 1 With a Urea Reduction Ratio ≥ 65% at Visits 2 and 3
Patients who experienced treatment failure at the end of Visit 1 and were eligible for and treated with extended-dwell tenecteplase at Visit 1 were assessed for Urea Reduction Ratio (URR) at Visits 2 and 3. URR was calculated from blood urea nitrogen (BUN) measurements according to the following:
(Pre-HD BUN) - (Post-HD BUN) * 100% / (Pre-HD BUN)
Measured: Blood urea nitrogen measurements were taken prior to HD and at the end of HD at Visits 2 (2nd HD session, within 72 hours after visit 1) and 3 (3rd HD session, within 72 hours of Visit 2)
Change in Blood Flow Rate From Baseline to the End of HD at Visit 2
Change in Blood flow rate (BFR) is the BFR at the end of HD for Visit 2 - BFR at Baseline.
Measured: Baseline (beginning of HD at Visit 1) to the end of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2006Oct 2008

First posted6 Nov 2006 (estimated)
Study startNov 2006
Primary completionOct 2008
Study completionOct 2008

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.
Other trials for Dysfunctional Hemodialysis CathetersStudies of the same condition, open and under way.
More trials run by Genentech, Inc.The sponsor's other registered studies.
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 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 223 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00396253
Sponsor's protocol ID: N3701g
Acronym: TROPICS 4
Status last verified: Nov 2016
First submitted: 2 Nov 2006
Last updated: 12 Jan 2017
Results posted: Yes, on ClinicalTrials.gov

Study at a glance

From the registry record, last updated by the sponsor on 12 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Open-Label Study of Tenecteplase for Restoration of Function in Dysfunctional Hemodialysis (HD) Catheters
ClinicalTrials.gov ID: NCT00396253
Acronym / sponsor ID: TROPICS 4 / N3701g
Conditions: Dysfunctional Hemodialysis Catheters
Keywords: HD, TNKase, Hemodialysis, Catheter clearance
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 223 participants (actual)
Lead sponsor: Genentech, Inc.Industry (pharma, biotech, devices)
Study start: Nov 2006
Primary completion: Oct 2008 (actual)
Study completion: Oct 2008 (actual)
First posted: 6 Nov 2006 (estimated)
Results: Posted 2 Aug 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Tenecteplase	Experimental	Drug: TenecteplaseAt each treatment, subjects had 2 mL (2 mg) of tenecteplase instilled into each lumen of their HD catheter. Subjects could receive up to three treatments with tenecteplase, the first two as part of the initial treatment course and one additional treatment as part of the retreatment (RT) course. The first treatment, followed by a 1-hour dwell time, was given to all subjects at Visit 1. At the end of hemodialysis at Visit 1, eligible subjects had a second treatment instilled for an extended dwell time until the start of Visit 2 (up to 72 hours).

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

Clinically stable, in the opinion of the investigator
Use of a cuffed, tunneled HD catheter
HD prescribed at a blood flow rate (BFR) of ≥300 mL/min
Baseline BFR (at any time during the first 60 minutes of HD) of <300 mL/min at an associated pre-pump negative arterial pressure in the range between and including -240 mmHg and -280 mmHg
Baseline BFR (at any time during the first 60 minutes of HD) at least 25 mL/min below the prescribed BFR

Key exclusion criteria (20 listed)

HD catheter with sustainable BFR of ≥300 mL/min following subject repositioning
HD catheter inserted <2 days prior to screening
Evidence of a mechanical, non-thrombotic cause of HD catheter dysfunction (e.g., kink in the catheter or suture constricting the catheter) or dysfunction caused by known fibrin sheath
Use of an implantable port
HD catheter that is internally coated with any therapeutic agent (e.g., the Decathlon™ Gold catheter)

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
Tenecteplase2 mL (2 mg) of reconstituted lyophilized tenecteplase instilled into each lumen of the HD catheter.	Drug	Tenecteplase

Primary outcome

Percentage of Participants Who Had Treatment Success With Respect to Blood Flow Rate (BFR) at Visit 1
Time frame: Visit 1 (the first hemodialysis session in which treatment was administered). BFR was measured at the beginning of hemodialysis (Baseline measurement) and at 30 minutes prior to the end of hemodialysis and at the end of hemodialysis.
Treatment success is defined as Blood Flow Rate (BFR) ≥ 300 mL/min and an increase of ≥ 25 mL/min from baseline BFR (without reversal of lines), at an associated arterial pressure in the range of 0 to -280 mmHg, 30 (± 10) minutes prior to the end of hemodialysis and at the end of hemodialysis.
Targeted Adverse Events From the Initial Study Drug Administration Through the Start of Visit 2 or Until Instillation of Extended-Dwell Tenecteplase
Time frame: From initial study drug administration to the end of Visit 1 (prior to administration of open-label, extended-dwell tenecteplase) or, for patients who did not receive extended-dwell tenecteplase, from initial study administration to the start of Visit 2.
The primary outcome measure was the number of targeted adverse events, occurring from initial study drug administration through the end of Visit 1 (prior to administration of open-label, extended-dwell tenecteplase) or, for subjects who did not receive open-label, extended-dwell tenecteplase, from initial study administration through the start of Visit 2. Targeted adverse events were defined as intracranial hemorrhage, major bleeding and embolic events, thrombosis, Catheter-related blood stream infection (CRBSIs), and catheter-related complications.

7 secondary outcomes

Percentage of Participants Who Maintained Catheter Function at Visits 2 and 3
Time frame: Maintenance BFR measurements were taken at the beginning of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1) and Visit 3 (3rd consecutive HD session, within 72 hours of Visit 2).
Percentage of Participants With Urea Reduction Ratio ≥ 65% at Visit 1
Time frame: At Visit 1 (first hemodialysis session in which treatment was administered) samples for blood urea nitrogen measurements were taken at the beginning of HD (prior to treatment administration) and after HD was completed.
Percentage of Participants With Urea Reduction Ratio ≥ 65% at Visit 2
Time frame: At Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1) samples for blood urea nitrogen measurements were taken prior to HD and after HD was completed.
Change in Blood Flow Rate From Baseline to the End of Hemodialysis at Visit 1
Time frame: Baseline (beginning of HD at Visit 1) to the end of HD at Visit 1.
Percentage of Participants Who Failed Treatment at Visit 1 With Treatment Success at Visit 2
Time frame: BFR was measured 30 minutes before the end of HD and at the end of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1). Baseline BFR was measured at the beginning of HD at Visit 1.
Percentage of Participants Who Failed Treatment at Visit 1 With a Urea Reduction Ratio ≥ 65% at Visits 2 and 3
Time frame: Blood urea nitrogen measurements were taken prior to HD and at the end of HD at Visits 2 (2nd HD session, within 72 hours after visit 1) and 3 (3rd HD session, within 72 hours of Visit 2)
Change in Blood Flow Rate From Baseline to the End of HD at Visit 2
Time frame: Baseline (beginning of HD at Visit 1) to the end of HD at Visit 2 (2nd consecutive HD session, within 72 hours of Visit 1).

Results and safety

Results posted to the registry on 2 Aug 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tenecteplase	223	210

Primary outcome: Percentage of Participants Who Had Treatment Success With Respect to Blood Flow Rate (BFR) at Visit 1

Time frame: Visit 1 (the first hemodialysis session in which treatment was administered). BFR was measured at the beginning of hemodialysis (Baseline measurement) and at 30 minutes prior to the end of hemodialysis and at the end of hemodialysis.. Number. Unit: Percentage of participants

Measure	Tenecteplase n = 223
Value	34.1

Population analysed: Modified intent to treat (MITT) population, consisting of all enrolled patients who received at least one dose of study drug (tenecteplase).

Primary outcome: Targeted Adverse Events From the Initial Study Drug Administration Through the Start of Visit 2 or Until Instillation of Extended-Dwell Tenecteplase

Time frame: From initial study drug administration to the end of Visit 1 (prior to administration of open-label, extended-dwell tenecteplase) or, for patients who did not receive extended-dwell tenecteplase, from initial study administration to the start of Visit 2.. Number. Unit: Events

Measure	Tenecteplase n = 223
Intracranial hemorrhage	0
Major bleeding	0
Embolic event	0
Thrombosis	1
Catheter-related blood stream infection	2
Catheter-related complication	0

Population analysed: Modified intent to treat (MITT) population

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Begins at initiation of study treatment and ends upon completion of the second visit following the last administration of study treatment or at early termination from the study, whichever is earlier.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tenecteplase	9 of 223 (4%)	36 of 223 (16.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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.

Barbara Gillespie, MD, FASN study director

Quintiles, Inc.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tenecteplase in people with Dysfunctional Hemodialysis Catheters, run by Genentech, Inc..

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 8 inclusion and 20 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 12 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 2 Aug 2011). 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?

Percentage of Participants Who Had Treatment Success With Respect to Blood Flow Rate (BFR) at Visit 1 (time frame: Visit 1 (the first hemodialysis session in which treatment was administered). BFR was measured at the beginning of hemodialysis (Baseline measurement) and at 30 minutes prior to the end of hemodialysis and at the end of hemodialysis.). The study lists 2 primary outcomes in all. 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 NCT00396253.

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 12 Jan 2017.