Clinical trial NCT00098007: A Study of Safety, Tolerability & Efficacy of Certican in de Novo Heart Transplant (Tx) Patients
Official title: Six-month, Multicenter, Randomized, Open-label Study of the Safety, Tolerability and Efficacy of Two Neoral Doses in Addition to Certican and Steroids in de Novo Heart Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Transplantation
Keywords: Heart transplantation
Everolimus
De novo heart transplant patients
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2004-12-02
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed to evaluate whether Neoral dose optimization together with a therapeutic drug monitoring of Certican will prevent renal dysfunction as observed in the pivotal cardiac trial while maintaining the efficacy.

This objective will be assessed by comparing renal function post-transplant between 2 groups of patients.


Eligibility criteria: Inclusion criteria Male or female cardiac patients 18-65 years old undergoing primary heart transplantation.

Females of potential childbearing age must have a negative serum pregnancy test within 7 days prior to enrollment. Effective contraception must be used during the trial and for 6 weeks following discontinuation of the study medication, even where there has been a history of infertility.

Patients who are willing and able to participate in the full course of the study and for whom written informed consent has been obtained.

Exclusion criteria Patients with donor hearts greater than 60 years of age and/or with a cold ischemia time of more than 6 hours and/or donor hearts which have obvious coronary disease or are known to have heart disease at time of transplant.

Patients who are recipients of multiple solid organ transplants, or who are previously received transplanted organs.

Patients who had received any investigational drug or who have been treated with an immunosuppressive drug treatment within 4 weeks prior to study entry.

Patients with serum creatinine level \> 250 mol/L. Patients with platelet count ≤ 50,000/mm3 or with a white blood cell count of ≤ 2,500/mm3.

Patients with active systemic infection, according to the investigator judgment, requiring continued therapy.

Patients with a known hypersensitivity to mTOR inhibitors. Patients with Panel Reactive Antibodies ≥ 25%. Presence of severe hypercholesterolemia (≥ 350mg/dL;≥9 mmol/L) or hypertriglyceridemia (≥ 750 mg/dL; ≥ 8.5 mmol/L).

Presence of any severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or hypersensitivity to drugs similar to Certican (e.g., macrolides).

Symptoms of a significant mental illness, which is in the opinion of the investigator may interfere with the patients ability to comply with the protocol. History of drug or alcohol abuse within 1 year of baseline.

Patients with any past (within the last 5 years) or present malignancy other than excised squamous or basal cell carcinoma.

Patients with any history of significant coagulopathy or medical condition requiring long-term anticoagulation after transplantation (low dose of aspirin treatment is allowed).

Abnormal physical or laboratory findings of clinical significance within 2 weeks prior to study entry which would interfere with the objectives of the study.

Inability to cooperate or communicate with the investigator. Female of childbearing potential to who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception.

Breast feeding women. Patients who are recipients of A-B-O incompatible transplants. Patients who are known to have chronic active Hepatitis C (PCR+ only), who are HIV or Hepatitis B surface antigen positive. Laboratory results obtained within 6 months prior to randomization are acceptable.

Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C (PCR+ only) are excluded

Primary outcomes:
measure: Renal function at 6 months post-transplant.
Secondary outcomes:
measure: Incidence of biopsy proven acute rejection ≥3A at 6 months.
measure: Incidence of acute rejection associated with hemodynamic compromise at 6 months.
measure: Incidence of graft loss at 6 months.
measure: Incidence of death at 6 months.
measure: Incidence of premature patient withdrawal and study treatment discontinuation at 6 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedar Sinai Medical Center
state: California
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: New York Presbyterian Medical Center
state: New York
city: Durham
country: United States
facility: Duke Clinical Research Institute
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Houston
country: United States
facility: Texas Heart Institute/St Lukes Hospital
state: Texas
city: Houston
country: United States
facility: The Baylor College of Medicine/ The Methodist Hospital
state: Texas
city: Milwaukee
country: United States
facility: St Luke's Medical Center
state: Wisconsin
city: Chermside
country: Australia
state: Queensland
city: Darlinghurst
country: Australia
city: Innsbruck
country: Austria
city: Vienna
country: Austria
city: Belo Horizonte
country: Brazil
state: MG
city: Sao Paulo
country: Brazil
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Hannover
country: Germany
city: Kiel
country: Germany
city: Milano
country: Italy
state: MI
city: Napoli
country: Italy
city: Barcelona
country: Spain
city: La Coruna
country: Spain
city: Llobregat
country: Spain
city: Oviedo
country: Spain
Study officials:
References:
citation: Zuckermann A, Wang SS, Ross H, Frigerio M, Eisen HJ, Bara C, Hoefer D, Cotrufo M, Dong G, Junge G, Keogh AM. Efficacy and Safety of Low-Dose Cyclosporine with Everolimus and Steroids in de novo Heart Transplant Patients: A Multicentre, Randomized Trial. J Transplant. 2011;2011:535983. doi: 10.1155/2011/535983. Epub 2011 Sep 13.