Study Comparing Effect On Carotid Atherosclerosis Following Conversion From Tacrolimus To Sirolimus Post-Transplant In Kidney Transplant Patients

This study has been terminated.

(See termination reason in detailed description.)

Sponsor:

Information provided by (Responsible Party):

Pfizer

ClinicalTrials.gov Identifier:

NCT00311311

First received: April 3, 2006

Last updated: May 15, 2012

Last verified: May 2012

History of Changes

Results First Received: December 12, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Atherosclerosis Kidney Failure
Interventions:	Drug: tacrolimus Drug: mycophenolate mofetil Drug: prednisone Drug: sirolimus

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

Description

Tacrolimus Then Sirolimus With Mycophenolate/Prednisone

Participant received tacrolimus (TAC), (target trough level of 3 to 10 nanograms per milliliter [ng/mL] by 3-4 months post transplant) plus mycophenolate mofetil (MMF) (greater than or equal to [>=] 500 milligram per day [mg/day]) or mycophenolate sodium (MPS) (>= 360 mg/day), plus prednisone, from day of transplant (Day 1) to 3-4 months post-transplant (Day 1 Conversion 0 to 14 days post randomization). Participants were randomized and assigned to treatment arms at Pre-Conversion Baseline (Weeks 12-24). On Day 1 Conversion the participant stopped or tapered off TAC and began conversion to sirolimus (SRL- target trough level 8-15ng/mL through month 24 post-transplant and 5-12ng/mL thereafter) + MMF (500-1500 mg/day) or MPS (360-1080 mg/day) + prednisone to end of study.

Tacrolimus With Mycophenolate/Prednisone

Participant received TAC , target trough level of 3 to 10 ng/mL by 3-4 months post-transplant to end of study plus MMF (>= 500 mg/day) or MPS (>= 360 mg/day) plus prednisone, from day of transplant (Day 1) to end of study.

Participant Flow: Overall Study

	Tacrolimus Then Sirolimus With Mycophenolate/Prednisone	Tacrolimus With Mycophenolate/Prednisone
STARTED	37	35
COMPLETED	19	15
NOT COMPLETED	18	20
Study Ongoing	13	17
Adverse Event	3	1
Withdrawal by Subject	1	1
Noncompliance	0	1
Death	1	0

Baseline Characteristics

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Reporting Groups

	Description
Tacrolimus Then Sirolimus With Mycophenolate/Prednisone	Participant received tacrolimus (TAC), (target trough level of 3 to 10 nanograms per milliliter [ng/mL] by 3-4 months post transplant) plus mycophenolate mofetil (MMF) (greater than or equal to [>=] 500 milligram per day [mg/day]) or mycophenolate sodium (MPS) (>= 360 mg/day), plus prednisone, from day of transplant (Day 1) to 3-4 months post-transplant (Day 1 Conversion 0 to 14 days post randomization). Participants were randomized and assigned to treatment arms at Pre-Conversion Baseline (Weeks 12-24). On Day 1 Conversion the participant stopped or tapered off TAC and began conversion to sirolimus (SRL- target trough level 8-15ng/mL through month 24 post-transplant and 5-12ng/mL thereafter) + MMF (500-1500 mg/day) or MPS (360-1080 mg/day) + prednisone to end of study.
Tacrolimus With Mycophenolate/Prednisone	Participant received TAC , target trough level of 3 to 10 ng/mL by 3-4 months post-transplant to end of study plus MMF (>= 500 mg/day) or MPS (>= 360 mg/day) plus prednisone, from day of transplant (Day 1) to end of study.
Total	Total of all reporting groups

Baseline Measures

	Tacrolimus Then Sirolimus With Mycophenolate/Prednisone	Tacrolimus With Mycophenolate/Prednisone	Total
Number of Participants [units: participants]	37	35	72
Age [units: years] Mean ± Standard Deviation	55.8 ± 11.11	55.5 ± 11.08	55.7 ± 11.02
Gender [units: participants]
Female	11	9	20
Male	26	26	52

Outcome Measures

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1. Primary:

Total Plaque Volume (TPV) Annual Rate of Change From Pre-conversion Baseline to 12 Months Post Transplant [ Time Frame: 12 Months Post-Transplant ]

Show Outcome Measure 1

2. Primary:

TPV at Pre-conversion Baseline [ Time Frame: Pre-Conversion Baseline ]

Show Outcome Measure 2

3. Secondary:

Carotid Intima Media Thickness (CIMT) Annual Rate of Change From Pre-conversion Baseline at 12, 18, 24 and 36 Months Post-transplant [ Time Frame: 12, 18, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 3

4. Secondary:

Change From Pre-conversion Baseline in Carotid Plaque Roughness at 12 and 24 Months Post-transplant [ Time Frame: Pre-Conversion Baseline, 12, and 24 Months Post-Transplant or ET ]

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5. Secondary:

Change From Pre-conversion Baseline in Fasting Lipid Parameters at 12 Months Post-transplant [ Time Frame: Pre-conversion baseline and 12 Months Post-Transplant ]

Show Outcome Measure 5

6. Secondary:

Change From Pre-conversion Baseline in Glucose at 12, 24, and 36 Months Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

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7. Secondary:

Change From Pre-conversion Baseline in Insulin at 12, 24, and 36 Months Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 7

8. Secondary:

Change From Pre-conversion Baseline in Hemoglobin (Hb) A1C at 12, 24, and 36 Months Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 8

9. Secondary:

Change From Pre-conversion Baseline in Adiponectin at Months 12, 24 and 36 Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

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Measure Type	Secondary
Measure Title	Change From Pre-conversion Baseline in Adiponectin at Months 12, 24 and 36 Post-transplant
Measure Description	Adiponectin is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates less risk. Change = month x post-transplant values - pre-conversion baseline values.
Time Frame	Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
On-Therapy Population; N=number of evaluable participants; n=number of evaluable participants at specific time point

Reporting Groups

Description

Tacrolimus Then Sirolimus With Mycophenolate/Prednisone

Tacrolimus With Mycophenolate/Prednisone

Measured Values

	Tacrolimus Then Sirolimus With Mycophenolate/Prednisone	Tacrolimus With Mycophenolate/Prednisone
Number of Participants Analyzed [units: participants]	21	33
Change From Pre-conversion Baseline in Adiponectin at Months 12, 24 and 36 Post-transplant [units: microgram per milliliter (µg/mL)] Mean ± Standard Deviation
Pre-Conversion Baseline (n=21,33)	13.786 ± 8.6745	15.575 ± 9.7513
Change at 12 Months Post-transplant (n=19, 31)	5.442 ± 5.6575	-2.348 ± 8.5005

Statistical Analysis 1 for Change From Pre-conversion Baseline in Adiponectin at Months 12, 24 and 36 Post-transplant

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.0008

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	12 months post-transplant
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value was estimated from ANCOVA model with baseline lab result as covariate. P-value was considered descriptive to illustrate strength of relationship rather than confirm hypotheses.

10. Secondary:

Change From Pre-conversion Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Months 12, 24 and 36 Post-transplant. [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 10

11. Secondary:

Change From Pre-conversion Baseline in Tumor Necrosis Factor Alpha (TNF-alpha) at Months 12, 24 and 36 Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 11

12. Secondary:

Change From Pre-conversion Baseline in Endothelin-1 at Months 12, 24 and 36 Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 12

13. Secondary:

Change From Pre-conversion Baseline in Interleukin-6 (IL-6) at Months 12, 24 and 36 Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 13

14. Secondary:

Change From Pre-conversion Baseline in Homocysteine at Months 12, 24 and 36 Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 14

15. Secondary:

Change From Pre-conversion Baseline in Lipoprotein (a) at Months 12, 24 and 36 Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 15

16. Secondary:

Change From Pre-conversion Baseline in Fibrinogen at Months 12, 24 and 36 Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 16

17. Secondary:

Change From Pre-conversion Baseline in Vitamin B12 at Months 12, 24 and 36 Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 17

18. Secondary:

Change From Pre-conversion Baseline in Uric Acid at Months 12, 24 and 36 Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 18

19. Secondary:

Change From Pre-conversion Baseline in Folate at 12, 24 and 36 Months Post-transplant [ Time Frame: Pre-conversion baseline, 12, 24 and 36 Months Post-Transplant or ET ]

Show Outcome Measure 19

20. Secondary:

Number of Participants Who Used Lipid Lowering or Anti-hypertensive Therapies [ Time Frame: 12 Months ]

Show Outcome Measure 20

21. Secondary:

CIMT at Pre-conversion Baseline [ Time Frame: Pre-Conversion Baseline ]

Show Outcome Measure 21

22. Other Pre-specified:

Change From Pre-conversion Baseline in Fasting Lipid Parameters at 1 and 6 Months Post-transplant [ Time Frame: 1 and 6 months post-conversion ]

Show Outcome Measure 22

23. Secondary:

Change From Pre-conversion Baseline in Fasting Lipid Parameters at 24 Months Post-transplant [ Time Frame: 24 Months Post-Transplant ]

Results not yet posted. Anticipated Posting Date: 12/2013 Safety Issue: Yes

24. Secondary:

Change From Pre-conversion Baseline in Fasting Lipid Parameters at 36 Months Post-transplant [ Time Frame: 36 Months Post-Transplant or ET ]

Results not yet posted. Anticipated Posting Date: 12/2013 Safety Issue: Yes

25. Secondary:

TPV Annual Rate of Change From Pre-conversion Baseline to 18, 24 and 36 Months Post Transplant [ Time Frame: Pre-Conversion Baseline, 18, 24, and 36 Month Post-Transplant or Early Termination (ET) ]

Results not yet posted. Anticipated Posting Date: 12/2013 Safety Issue: Yes

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Scheduled completion first quarter 2013, primary completion date was 12 months post-transplant (PT), only information up to 12 months PT reported. Statistical Analysis Plan detailed changes from Protocol in analysis of primary/secondary endpoints.

Results Point of Contact:

Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00311311 History of Changes
Other Study ID Numbers:	0468H1-319
Study First Received:	April 3, 2006
Results First Received:	December 12, 2011
Last Updated:	May 15, 2012
Health Authority:	Canada: Health Canada

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