Ignite Creation Date:
2024-05-05 @ 4:53 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00338455
Status:
TERMINATED
Last Update Posted:
2014-12-08
First Post:
2006-06-16
Brief Title:
Natrecor Nesiritide in Transplant-Eligible Management of Congestive Heart Failure-TMAC
Sponsor:
Scios Inc
Organization:
Scios Inc
Study Overview
Official Title:
Investigation of the Use of Natrecor Nesiritide in Transplant-Eligible Management of Congestive Heart Failure-TMAC
Status:
TERMINATED
Status Verified Date:
2014-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
DSMC acknowledged no safety concerns with the trial recommending that the trial be terminated due to slow enrollment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purposes of this study in United Network for Organ Sharing UNOS Status 1B or country equivalent cardiac transplant candidates are to assess the safety and efficacy of Natrecor nesiritide The study will evaluate the drugs ability to prevent clinical worsening when administered as a 28-day continuous intravenous infusion in patients receiving standard care and continuous intravenous infusion of dobutamine or milrinone
Detailed Description:
Endogenous B-type natruretic peptide BNP concentrations correlate with heart failure HF severity and are significantly elevated in severe end-stage HF patients However normal biologic compensatory responsiveness to BNP is attenuated in patients with severe HF Patients who are UNOS 1B cardiac transplant candidates have relatively few options for therapy despite the fact that they constitute a very ill patient population These options include getting a transplant if one is available receiving intravenous inotropes andor vasodilators or being implanted with a circulatory support device eg Left Ventricular Assist Device Natrecor Nesiritide is a human recombinant form of BNP approved for use in the treatment of acute decompensated HF Limited information is available from controlled clinical trials on the effects of Natreor nesiritide infusion for longer than 72 hours However based on reports in the literature Natrecor nesiritide has been used by independent investigators for much longer durations in end-stage HF patients including UNOS Status 1B cardiac transplant candidates who are refractory to standard care In these patients Natrecor nesiritide has been safely administered by continuous infusion for more than 2 and up to 210 days These experiences showed that continuous Natrecor nesiritide infusion was well tolerated uniformly improved hemodynamics circulation of the blood and the forces involved maintained stable renal kidney function and reduced the need for ventricular assist devices during the prolonged wait for heart transplant In controlled clinical trials reported in literature Natrecor nesiritide was given concomitantly with several other standard HF therapeutic agents such as diuretics angiotensin-converting enzyme ACE inhibitors beta-blockers dopamine dobutamine anticoagulants digoxin and oral nitrates Concomitant dosing was well tolerated and no drug interactions were observed No randomized controlled trial has been conducted to evaluate the safety of combination nesiritide and milrinone therapy Several investigations were undertaken because of concerns over the potential additive hypotensive lowering blood pressure effect that these two agents may exert when administered concurrently The study investigators reported that concurrent dosing of milrinone and nesiritide appeared to be safe and beneficial without evidence of an additive hypotensive lowering blood pressure effect The TMAC trial will investigate the safety and efficacy of Natrecor nesiritide compared with placebo when added to standard care in the management of end-stage refractory HFThis prospective randomizedpatients are assigned different treatments based on chance parallel multicenter double-blind neither the doctor nor the patient knows whether the patient is being administered a placebo or the test drug placebo-controlled study will be conducted with UNOS Status 1B or equivalent cardiac transplant candidates who are receiving standard care and continuous IV infusion of dobutamine or milrinone while awaiting heart transplantation Approximately 120 patients will participate in this study Enrolled patients will be randomized 11 to receive Natrecor nesiritide by continuous infusion in addition to standard care and one inotrope drugs such as dobutamine or milrinone used to increase the heart rate and improve the force of cardiac contraction or to receive placebo by continuous infusion in addition to standard care and one inotrope dobutamine or milrinone Patients will be managed as inpatients or outpatients according to the guidelines in this protocol and study center practices All patients will continue to receive their usual long-term cardiac medications excluding commercial nesiritide Study drug dose adjustments may be made according to the guidelines in this protocol and the investigators clinical judgment and in accordance with the dosing guidelinesStudy drug will be administered as a continuous intravenous infusion under the control of a programmable ambulatory infusion pump for the 28-day treatment period Patients will be hospitalized for study drug initiation and titration to ensure safety observe tolerability and achieve the recommended study drug dose Day 0 Screening will entail completing required procedures and randomization Baseline and screening procedures may occur on the same day A window of up to 7 days will be permitted between Day 0 Screening and Day 1 Baseline visits if circumstances delay initiation of study drug dosing The following day Day 1 Baseline continuous infusion of study drug will begin Patients will be hospitalized for a minimum of 3 days after starting the study drug for titration and dose optimization A dose optimization period of up to 5 days will be permitted Patients will be eligible for discharge following completion of the study procedures on the 4th dosing day Day 4 Patients will return to the clinic for weekly visits 2 days through Day 28 Termination of Treatment and again at Day 35 for a 7-day post dosing safety visit On the Day 28 visit Termination of Treatment Patients may be hospitalized for up to 24 hours at the investigators discretion to undergo end of treatment study procedures This study includes two substudies the Pulmonary Function Testing Substudy and the Glomerular Filtration Rate Substudy All TMAC Patients will be asked to participate in these substudies Participation is optional and does not affect enrollment or participation in TMAC The Study Hypothesis is that continuous administration of Natrecor nesiritide over 28 days when added to standard care including inotropes is safe and provides a clinical benefit when compared to placebo added to standard care including inotropes therapy Study drug will be administered continuously as a fixed-rate infusion for 28 days without a bolus dose Natrecor nesiritide dosing will begin at 0005 mcgkgmin and may be titrated to a maximum dose of 0015 mcgkgmin
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| TMAC | None | None | None |
| A051 | None | None | None |