Conversion From MPA to Zortress (Everolimus) for GI Toxicity Post-renal Transplantation

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02974686
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 1
• Location: 1
• Arms: 2
• Actual Duration (Months): 34
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Patients who receive renal transplantation at Barnes Jewish Hospital (BJH) are placed on triple maintenance immunosuppression, which means that patients take 3 types of immunosuppression drugs to suppress their immune system including tacrolimus, mycophenolate (MPA), and prednisone. However, due to the effects of MPA on the gastrointestinal tract, patients often complain of GI adverse effects. Current practice is to either dose-reduce MPA or convert the patient to an alternative agent, typically Azathioprine. Both of these strategies have limitations, largely due to concerns related to efficacy. Everolimus (EVR) has demonstrated similar efficacy to MPA in renal transplantation and may offer a benefit related to GI adverse effects, so the investigators will convert patients to EVR in this study. Patients who are within their first year post-transplant will be converted to EVR upon enrollment in the study, and serial measurements ,or a series of measurements looking for an increase or decrease over time, of GI adverse effects will be conducted over 1 year post-enrollment.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant Rejection; Gastrointestinal Disorder, Functional	Drug: Everolimus; Drug: Mycophenolic Acid	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Conversion From MPA to Zortress (Everolimus) for GI Toxicity Post-renal Transplantation
• Actual Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Sep 1, 2019
• Actual Study Completion Date: Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Interventional (EVR) Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus	Drug: Everolimus; Other Names: Zortress
Active Comparator: Prior Agent (MPA) Patient will have baseline data collected while on MPA for comparison with EVR	Drug: Mycophenolic Acid; Other Names: Cellcept Myfortic

Outcome Measures

Primary Outcome Measures

1. Gastrointestinal Symptom Rating Scale [3 months]

   Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.

Secondary Outcome Measures

1. Gastrointestinal Symptom Rating Scale [1, 6, and 12 months]

   Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.

2. Biopsy Proven Acute Rejection [12 months]

   Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Kidney transplant recipients at Washington University/Barnes-Jewish Hospital

2. Experiencing GI toxicity from MPA as determined by the treating physician within 12 months post-renal transplant

3. On standard immunosuppression with tacrolimus and prednisone

Exclusion Criteria:

1. Dual organ or kidney after another solid organ transplant

2. Presence of a preexisting significant GI condition that does not have a presumed causal relationship with MPA

3. Evidence of any GI disorder induced by an infection, underlying medical condition, or concomitant medication other than MPA

4. Estimated glomerular filtration rate (eGFR) <40 ml/min at time of possible conversion

5. Proteinuria >1 gram/day at time of possible conversion

6. Profound bone marrow suppression at the time of possible conversion as defined as:

• Hemoglobin <10 g/dL

• White blood cell (WBC) < 3 K/cumm

• Platelets <100 K/cumm

1. Wound healing issues at time of possible conversion (eg, wound dehiscence, wound infection, incisional hernia, lymphocele, seroma)

2. Elevated total cholesterol (>350 mg/dL) and/or triglycerides (>500 ng/dL) at time of possible conversion

3. Hypersensitivity to everolimus, sirolimus, or other rapamycin derivatives

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 31, 2018

More Information

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02974686
• Other Study ID Numbers: 201603167; CRAD001AUS209T
• First Posted: Nov 28, 2016
• Last Update Posted: Aug 10, 2020
• Last Verified: Aug 1, 2020

• Additional relevant MeSH terms: Gastrointestinal Diseases; Digestive System Diseases; Mycophenolic Acid; Everolimus

Study Results

Participant Flow

Pre-assignment Detail	Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.

Arm/Group Title	Interventional Everolimus (EVR)	Prior Agent Mycophenolic Acid (MPA)
Arm/Group Description	Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus Everolimus	Patient will have baseline data collected while on MPA for comparison with EVR Mycophenolic Acid
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Interventional (EVR)	Prior Agent (MPA)	Total
Arm/Group Description	Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus Everolimus	Patient will have baseline data collected while on MPA for comparison with EVR Mycophenolic Acid	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age () []
Sex: Female, Male () []
Female
Male
Race (NIH/OMB) () []
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

Title	Gastrointestinal Symptom Rating Scale
Description	Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.

Arm/Group Title	Interventional (EVR)	Prior Agent (MPA)
Arm/Group Description	Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus Everolimus	Patient will have baseline data collected while on MPA for comparison with EVR Mycophenolic Acid
Measure Participants	0	0

2. Secondary Outcome

Title	Gastrointestinal Symptom Rating Scale
Description	Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.
Time Frame	1, 6, and 12 months

Outcome Measure Data

Analysis Population Description

Trial was terminated with only 1 participant enrolled, no data is reported to protect patient confidentiality

Arm/Group Title	Interventional (EVR)	Prior Agent (MPA)
Arm/Group Description	Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus Everolimus	Patient will have baseline data collected while on MPA for comparison with EVR Mycophenolic Acid
Measure Participants	0	0

3. Secondary Outcome

Title	Biopsy Proven Acute Rejection
Description	Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Trial was terminated with only 1 participant enrolled, no data is reported to protect patient confidentiality

Arm/Group Title	Interventional Everolimus (EVR)	Prior Agent Mycophenolic Acid (MPA)
Arm/Group Description	Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus Everolimus	Patient will have baseline data collected while on MPA for comparison with EVR Mycophenolic Acid
Measure Participants	0	0

Adverse Events

Time Frame	Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.
Adverse Event Reporting Description	Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.
Arm/Group Title	Interventional (EVR)		Prior Agent (MPA)
Arm/Group Description	Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus Everolimus		Patient will have baseline data collected while on MPA for comparison with EVR Mycophenolic Acid
All Cause Mortality
	Interventional (EVR)		Prior Agent (MPA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Interventional (EVR)		Prior Agent (MPA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Interventional (EVR)		Prior Agent (MPA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.

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.