Everolimus in de Novo Heart Transplant Recipients | NCT01017029

ID	Type	Description	Link
2009-011008-43

Everolimus in de Novo Heart Transplant Recipients | NCT01017029 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Immediate introduction of everolimus	Active Comparator		Drug: Everolimus
Delayed introduction of everolimus	Experimental	delayed introduction) + Cyclosporin + steroids	Drug: Mycophenolate mofetil + Everolimus

Name	Type	Description	Arm Group Labels	Other Names
Everolimus	Drug		Immediate introduction of everolimus
Mycophenolate mofetil + Everolimus

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Participants With at Least One Occurrence of Safety Composite Endpoint After 6 Months by Treatment Group	Comparison of 6-month cumulative incidence of safety composite endpoint (wound healing delay) related to initial transplant surgery, pleural/pericardial effusions and occurrence of acute renal insufficiency, defined as estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2, between delayed everolimus arm and immediate everolimus arm	6 months

Secondary Outcomes

Measure	Description	Time Frame
Partcipants With at Least One Occurrence of Each Safety Composite Endpoint Event After 6 Months by Treatment Group		6 months
Hazard Cox's Model Analysis of Pericardial/Pleural Effusions	Pericardial effusions: any pericardial effusion defined as at least moderate (i.e. measuring at least 2.0 cm in diastole, in the point of largest distance between the pericardial leaflets), with or without signs of hemodynamic compromise, or leading to drainage or to prolonged hospitalization. Pleural effusions: need for surgical drainage tubes for longer than 7 days after surgery and subsequent pleural effusions leading to drainage. CI = confidence interval, HR = hazard ratio, MDRD = Modification of Diet in Renal Disease

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Bari	BA	70124	Italy
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28930797	Derived	Potena L, Pellegrini C, Grigioni F, Amarelli C, Livi U, Maccherini M, Masciocco G, Faggian G, Lilla Della Monica P, Gerosa G, Marraudino N, Corda M, Boffini M; EVERHEART Investigators. Optimizing the Safety Profile of Everolimus by Delayed Initiation in De Novo Heart Transplant Recipients: Results of the Prospective Randomized Study EVERHEART. Transplantation. 2018 Mar;102(3):493-501. doi: 10.1097/TP.0000000000001945.

Arm/Group Information

ID	Title	Description
FG000	Immediate Introduction of Everolimus	Everolimus within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids
FG001	Delayed Introduction of Everolimus	Mycophenolate mofetil (MMF) within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids. After 4 to 6 weeks since transplant, everolimus in place of MMF and dose of cyclosporine reduced.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00089 subjects FG00192 subjects
COMPLETED		FG00085 subjects FG00190 subjects
NOT COMPLETED		FG0004 subjects FG0012 subjects

Type	Comment	Reasons
Lost to Follow-up		FG0001 subjects FG0010 subjects
Administrative problem		FG0000 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Immediate Introduction of Everolimus	Everolimus within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids
BG001	Delayed Introduction of Everolimus

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Participants With at Least One Occurrence of Safety Composite Endpoint After 6 Months by Treatment Group

Comparison of 6-month cumulative incidence of safety composite endpoint (wound healing delay) related to initial transplant surgery, pleural/pericardial effusions and occurrence of acute renal insufficiency, defined as estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2, between delayed everolimus arm and immediate everolimus arm

safety population

Posted

Number

95% Confidence Interval

participants

6 months

ID	Title	Description
OG000	Immediate Introduction of Everolimus	Everolimus within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids
OG001	Delayed Introduction of Everolimus

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Immediate Introduction of Everolimus	Everolimus within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Leukopenia	Blood and lymphatic system disorders	17.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	17.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Novartis	Pharmaceuticals	+1(862)778-8300

Intervention Browse Module

ID	Term
D000068338	Everolimus
D009173	Mycophenolic Acid

ID	Term
D020123	Sirolimus
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D002208

Calculated BMI

Body Mass Index (BMI) Body mass divided by the square of their height.

Mean

Standard Deviation

kg/m2*

Title

Denominators

Categories

Title	Measurements
	BG00025.44± 3.65 BG00124.48± 3.33 BG00224.95± 3.52

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Cox		0.1043		Hazard Ratio (HR)	1.482			2-Sided	95	0.922	2.383				No	Superiority or Other

Secondary

Partcipants With at Least One Occurrence of Each Safety Composite Endpoint Event After 6 Months by Treatment Group

safety population

Posted

Number

95% Confidence Interval

participants

6 months

participants

Participants

ID	Title	Description
OG000	Immediate Introduction of Everolimus	Everolimus within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids
OG001	Delayed Introduction of Everolimus	Mycophenolate mofetil (MMF) within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids. After 4 to 6 weeks since transplant, everolimus in place of MMF and dose of cyclosporine reduced.

Units	Counts
Participants	OG00089 OG00192

Title

Denominators

Categories

Wound healing complication

Title	Measurements
	OG00010(4.7 to 17.8) OG0018(2.9 to 14.50)

Pleural effusion

Title	Measurements
	OG000

Secondary

Hazard Cox's Model Analysis of Pericardial/Pleural Effusions

Pericardial effusions: any pericardial effusion defined as at least moderate (i.e. measuring at least 2.0 cm in diastole, in the point of largest distance between the pericardial leaflets), with or without signs of hemodynamic compromise, or leading to drainage or to prolonged hospitalization. Pleural effusions: need for surgical drainage tubes for longer than 7 days after surgery and subsequent pleural effusions leading to drainage. CI = confidence interval, HR = hazard ratio, MDRD = Modification of Diet in Renal Disease

safety population

Posted

Number

participants

6 months

ID	Title	Description
OG000	Immediate Introduction of Everolimus	Everolimus within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids
OG001	Delayed Introduction of Everolimus	Mycophenolate mofetil (MMF) within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids. After 4 to 6 weeks since transplant, everolimus in place of MMF and dose of cyclosporine reduced.

Units	Counts
Participants	OG00089 OG00187

Title

Denominators

Categories

Title	Measurements
	OG00030 OG00118

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Cox		0.0398		Hazard Ratio (HR)	1.847			2-Sided	95	1.029	3.315				No	Superiority or Other

Secondary

Absolute and Percent Frequencies of Patients With LDL ≥ 100 mg/mL at 1, 3 and 6 Months, by Treatment Group

LDL = low density lipoprotein

safety population

Posted

Number

95% Confidence Interval

participants

6 months

ID	Title	Description
OG000	Immediate Introduction of Everolimus	Everolimus within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids
OG001	Delayed Introduction of Everolimus	Mycophenolate mofetil (MMF) within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids. After 4 to 6 weeks since transplant, everolimus in place of MMF and dose of cyclosporine reduced.

Units	Counts
Participants	OG00089 OG00192

Title

Denominators

Categories

Month 1

Title	Measurements
	OG00041(35.70 to 56.40) OG00138(31.60 to 51.90)

Month 3

Title	Measurements
	OG000

Secondary

Participants With CMV Infection and CMV Syndrome/Disease After 6 Months by Treatment Group

CMV infection is defined as pp65 antigenemia or DNAemia

safety population

Posted

Number

95% Confidence Interval

participants

6 months

ID	Title	Description
OG000	Immediate Introduction of Everolimus	Everolimus within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids
OG001	Delayed Introduction of Everolimus	Mycophenolate mofetil (MMF) within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids. After 4 to 6 weeks since transplant, everolimus in place of MMF and dose of cyclosporine reduced.

Units	Counts
Participants	OG00089 OG00192

Title

Denominators

Categories

CMV infections

Title	Measurements
	OG00046(41.30 to 62.10) OG00163(59.00 to 78.00)

CMV syndrome/disease

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	CMV infections	Fisher Exact		0.0234													No	Superiority or Other

Secondary

Participants With at Least One Occurrence of Composite Treatment Failure Events

Comparison of 6-months cumulative incidence of composite treatment failure events (BPAR ≥ 2R, rejection with hemodynamic compromise, graft loss, or death) between delayed everolimus arm and immediate everolimus arm

Posted

Number

95% Confidence Interval

participants

6 months

ID	Title	Description
OG000	Immediate Introduction of Everolimus	Everolimus within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids
OG001	Delayed Introduction of Everolimus	Mycophenolate mofetil (MMF) within 144 hours (5 days) after graft reperfusion + cyclosporine microemulsion + steroids. After 4 to 6 weeks since transplant, everolimus in place of MMF and dose of cyclosporine reduced.

Units	Counts
Participants	OG00089 OG00192

Title

Denominators

Categories

Title	Measurements
	OG00033(27.00 to 47.10) OG00126(19.10 to 37.50)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Cox		0.1966		Hazard Ratio (HR)	1.403			2-Sided	95	0.839	2.347				No	Superiority or Other