Clinical trial NCT00271167: A Trial of INO-1001 in Patients Undergoing Heart Surgery That Involves Heart-lung Bypass
Official title: A Phase II Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate Tolerability, Safety, Pharmacokinetics and Efficacy of Intravenous INO-1001 in High Risk Subjects Undergoing Cardiopulmonary Bypass for Coronary Revascularization and/or Valve Surgery.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Heart Diseases
Postoperative Complications
Keywords: Cardiac surgery
PARP inhibitor
PARP inhibition
Bypass surgery
CPB surgery
Cardiopulmonary bypass
Coronary revascularization
Cardiac valve replacement
Lead sponsor: Inotek Pharmaceuticals Corporation
Sponsor class: INDUSTRY
First posted: 2005-12-30
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety of INO-1001, an intravenous PARP (poly-\[ADP ribose\] polymerase) inhibitor, in patients undergoing heart surgery. The study also measures whether INO-1001 reduces the side effects caused by heart-lung bypass machines.

Detailed description: Heart-lung bypass during heart surgery sometimes leads to side effects or complications after surgery.

Studies have shown that PARP inhibitors protect cells from damage due to lack of oxygen. Heart-lung bypass during heart surgery can result in cells being deprived of oxygen. INO-1001 may be able to protect these cells and reduce complications following surgery.

A total of 162 patients will be randomly assigned to either INO-1001 or placebo (sugar water). Treatment will begin on the day of heart surgery and continue for 36 hours. A total of 4 doses of INO-1001 will be given. Patients will be followed up until 30 days after surgery.

The following information will be collected: symptoms, vital signs, physical examination, blood and urine tests, electrocardiograms, and other information from medical charts.

The information provided in this listing is disclosed solely to comply with regulatory requirements. The drug INO-1001 has not yet been approved for marketing and is only available to patients who participate in a clinical trial and are chosen for the treatment group.

Eligibility criteria: Inclusion Criteria:

* Patients scheduled to undergo cardiopulmonary bypass for coronary revascularization and/or valve surgery
* Males and non-pregnant, non-lactating females

Exclusion Criteria:

* Subjects will be required to undergo a full medical review in order to exclude serious medical or psychological illness prior to inclusion
* History of a hypersensitivity reaction to more than three drugs or to mannitol
* Participation in any other investigational study within 30 days of the screening phase
* Known alcohol or drug abuse within the last year
* Treatment with certain restricted medications within a specified time prior to participation in the study

Primary outcomes:
measure: Reduction in serious post-operative complications occurring in the first thirty days after surgery.
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Oklahoma
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Sydney
country: Australia
state: New South Wales
city: Adelaide
country: Australia
facility: Ashford Cardiac Clinic / Adelaide Cardiac
state: South Australia
city: Melbourne
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Hyderabad
country: India
facility: Care Hospital
city: New Delhi
country: India
facility: Escorts Heart Institute and Research Centre
city: Holon
country: Israel
facility: Wolfson Medical Centre
city: Jerusalem
country: Israel
Study officials:
References:
citation: Khan TA, Ruel M, Bianchi C, Voisine P, Komjati K, Szabo C, Sellke FW. Poly(ADP-ribose) polymerase inhibition improves postischemic myocardial function after cardioplegia-cardiopulmonary bypass. J Am Coll Surg. 2003 Aug;197(2):270-7. doi: 10.1016/S1072-7515(03)00538-6.
citation: Virag L, Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev. 2002 Sep;54(3):375-429. doi: 10.1124/pr.54.3.375.
citation: Szabo C. Pharmacological inhibition of poly(ADP-ribose) polymerase in cardiovascular disorders: future directions. Curr Vasc Pharmacol. 2005 Jul;3(3):301-3. doi: 10.2174/1570161054368553.