PPM - Pro: Optimizing Immunosuppression Drug Dosing Via Phenotypic Precision Medicine

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT03527238
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 62
• Locations: 3
• Arms: 2
• Actual Duration (Months): 35.3
• Patients Per Site: 20.7
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Clinical trial applying Phenotypic Precision Medicine (PPM) to tacrolimus dosing in liver and/or kidney transplant recipients to show improvement in maintaining drug trough levels within the target range.

Condition or Disease	Intervention/Treatment	Phase
Liver Transplant; Kidney Transplant	Other: PPM-based Computation Assisted Drug Dosing; Drug: Tacrolimus	Phase 2

Detailed Description

The introduction of calcineurin inhibitors like tacrolimus has greatly reduced the incidence of acute rejection, improving graft and patient survival after transplantation. However, tacrolimus, one of the most widely used immunosuppressants and a mainstay of solid organ transplantation, has a narrow therapeutic index and wide pharmacokinetic variability. As such, there is a clear need for precision medicine to address post-transplant immunosuppression.

The study team has developed a powerful platform [Phenotypic Precision Medicine (PPM)] that utilizes patient-specific clinical data which represents each patient's response to drug treatment. This platform can efficiently prescribe precise and optimized drug doses despite the frequent changes to patient treatment regimens following transplantation. This potentially can have a profound effect on drug metabolism.

The aim of this project is to use PPM to uncover valuable and previously unknown information pertaining to patient dose requirements and correlate them with patient clinical and other contextual information. This study is also expected to reveal vital patient subpopulation information; and any future discovery of quantitative biomarkers as measures of immunosuppression will serve as a gateway towards even more effective personalized and relevant drug dosing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Supportive Care
• Official Title: Optimizing Immunosuppression Drug Dosing Via Phenotypic Precision Medicine
• Actual Study Start Date: Sep 21, 2018
• Actual Primary Completion Date: Jun 2, 2020
• Actual Study Completion Date: Aug 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard of Care Standard of Care Tacrolimus Drug Dosing	Drug: Tacrolimus; Dosing of calcineurin inhibitor, tacrolimus
Experimental: Phenotypic Precision Medicine (PPM) PPM-based Computation Assisted Drug Dosing	Other: PPM-based Computation Assisted Drug Dosing; Tacrolimus dosing based on application of PPM.; Other Names: Computation based dosing ; Drug: Tacrolimus; Dosing of calcineurin inhibitor, tacrolimus

Outcome Measures

Primary Outcome Measures

1. Tacrolimus Target Trough Level Maintenance [2 weeks]

   Percentage of Days Far (> 2 ng/mL) Out of Range of Tacrolimus Target Trough Level

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• adults undergoing liver and/or kidney transplantation

Exclusion Criteria:

• transplant patients with contraindications to tacrolimus

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA	Los Angeles	California	United States	90095
2	UF Health at the University of Florida	Gainesville	Florida	United States	32610
3	National University of Singapore	Singapore		Singapore	119077

Sponsors and Collaborators

• University of Florida
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Ali Zarrinpar, MD PhD, University of Florida

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jun 5, 2019

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT03527238
• Other Study ID Numbers: IRB201800053 -N -A; 1R21DK116140-01
• First Posted: May 17, 2018
• Last Update Posted: Dec 10, 2021
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Florida: Phenotypic Precision Medicine (PPM); Tacrolimus; Calcineurin Inhibitors
• Additional relevant MeSH terms: Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Standard of Care	Phenotypic Precision Medicine (PPM)
Arm/Group Description	Standard of Care Tacrolimus Drug Dosing Tacrolimus: Dosing of calcineurin inhibitor, tacrolimus	PPM-based Computation Assisted Drug Dosing PPM-based Computation Assisted Drug Dosing: Tacrolimus dosing based on application of PPM. Tacrolimus: Dosing of calcineurin inhibitor, tacrolimus
Period Title: Overall Study
STARTED	31	31
COMPLETED	29	27
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Standard of Care	Phenotypic Precision Medicine (PPM)	Total
Arm/Group Description	Standard of Care Tacrolimus Drug Dosing Tacrolimus: Dosing of calcineurin inhibitor, tacrolimus	PPM-based Computation Assisted Drug Dosing PPM-based Computation Assisted Drug Dosing: Tacrolimus dosing based on application of PPM. Tacrolimus: Dosing of calcineurin inhibitor, tacrolimus	Total of all reporting groups
Overall Participants	31	31	62
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	26 83.9%	25 80.6%	51 82.3%
>=65 years	5 16.1%	6 19.4%	11 17.7%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	57	58	57.5
Sex: Female, Male (Count of Participants)
Female	14 45.2%	13 41.9%	27 43.5%
Male	17 54.8%	18 58.1%	35 56.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.5%	4 12.9%	6 9.7%
Not Hispanic or Latino	29 93.5%	27 87.1%	56 90.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 3.2%	1 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 6.5%	0 0%	2 3.2%
White	29 93.5%	30 96.8%	59 95.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	31 100%	31 100%	62 100%

Outcome Measures

1. Primary Outcome

Title	Tacrolimus Target Trough Level Maintenance
Description	Percentage of Days Far (> 2 ng/mL) Out of Range of Tacrolimus Target Trough Level
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard of Care	Phenotypic Precision Medicine (PPM)
Arm/Group Description	Standard of Care Tacrolimus Drug Dosing Tacrolimus: Dosing of calcineurin inhibitor, tacrolimus	PPM-based Computation Assisted Drug Dosing PPM-based Computation Assisted Drug Dosing: Tacrolimus dosing based on application of PPM. Tacrolimus: Dosing of calcineurin inhibitor, tacrolimus
Measure Participants	29	27
Mean (Standard Deviation) [percentage of days]	38.4 (27.4)	24.2 (19.1)

Adverse Events

Time Frame	30 days after discharge
Arm/Group Title	Standard of Care		Phenotypic Precision Medicine (PPM)
Arm/Group Description	Standard of Care Tacrolimus Drug Dosing Tacrolimus: Dosing of calcineurin inhibitor, tacrolimus		PPM-based Computation Assisted Drug Dosing PPM-based Computation Assisted Drug Dosing: Tacrolimus dosing based on application of PPM. Tacrolimus: Dosing of calcineurin inhibitor, tacrolimus
All Cause Mortality
	Standard of Care		Phenotypic Precision Medicine (PPM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/31 (0%)
Serious Adverse Events
	Standard of Care		Phenotypic Precision Medicine (PPM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Standard of Care		Phenotypic Precision Medicine (PPM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/31 (19.4%)		6/31 (19.4%)
Immune system disorders
Rejection	6/31 (19.4%)	6	6/31 (19.4%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.