Medication AdherencePhase 3AdvagrafNCT02805842
Incidence of Non Adherence to Treatment With Once-daily Formulation of Tacrolimus
A Phase 3 study testing Tacrolimus BID and Advagraf QD in people with Medication Adherence, run by Rabin Medical Center at 1 site in Israel.
Trial summary
Aim The primary objective of this study is to compare medication adherence with medical therapy in patients receiving once-daily versus twice-daily tacrolimus regimens. Participants 60 adult renal transplant patients randomized 1:2 into twice-daily and once-daily tacrolimus groups Outcomes The primary outcome will be… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Medication Adherence
- What is being tested?
- Tacrolimus BID and Advagraf QD
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIsrael
- Study dates
- Aug 2016to Aug 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age: 18 Years to 60 Years
- Gender: both
- Patients willing and able to participate in this study
- Patients who signed the informed consent form
- Patients who can visit the center based on the study schedule in the protocol
Who cannot join
- Patients who had previously received a kidney or another organ
- Patients, having positive lymphocyte cross-match
- Patients with PRA >50%
- Patients, who underwent desensitization
- Patients, who were diagnosed with cancer in the last five years
- Patients, who themselves or their donors have positive HIV, HBsAg, or anti-HCV test results
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- Patients, who were treated with other investigated drugs within 30 days from their study enrollment
- Patients, who are planning to be pregnant, or who are pregnant or breastfeeding and who are not planning to use any contraceptive method during the study period.
- Patients who were addicted to drugs/alcohol within six months of their study enrollment
- Patients, who have a mental illness that makes appropriate communication with them impossible
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Incidence of Non Adherence to Treatment With Once-daily Formulation of Tacrolimus (ADVAGRAF) in Kidney Transplant Recipients
Aim The primary objective of this study is to compare medication adherence with medical therapy in patients receiving once-daily versus twice-daily tacrolimus regimens.
Participants 60 adult renal transplant patients randomized 1:2 into twice-daily and once-daily tacrolimus groups
Outcomes The primary outcome will be medication adherence to the once-daily and twice-daily regimens, measured in terms of implementation. Secondary outcomes will include graft and patient survival, renal function and adverse events. Follow up - 12 months
Read the detailed description
Following randomization (Day 0), 60 kidney transplant recipients of deceased or live kidneys will be randomized 1:2 into control and study- experimental arm. In control arm, named Tacrolimus BID arm, tacrolimus will be administered unchanged twice daily, morning and evening, while in study--experimental group named Tacrolimus QD- Advagraf, the Advagraf tacrolimus formulation will be administered once daily in the morning. In both groups doses will be adjusted to maintain tacrolimus trough levels at 10-12 ng/mL (days 1-28), 8-10 ng/mL (days 29-168) and 6-8 ng/mL thereafter for both treatment arms.
Adjunct immunosuppression. Per-protocol rejection prophylaxis: All patients will receive Basiliximab induction at 20mg/bw on days 0 and 4. Methylprednisolone will be administered as intravenous bolus doses of 500 mg , 250 mg and 125 mg perioperatively, on days 0,1 and 2. Thereafter oral prednisone will be given: 20 mg/day (days 2-14), 15 mg/day (days 15-30), 10 mg/day (days 30-45), 7.5 mg/day (days 45-60) and 5 mg/day thereafter. MMF (2 g BID) will be started preoperatively, and reduced to 500 mg three times daily after 14-30 days.
Rejection treatment: First-line acute rejection (AR) therapy with corticosteroids will be administered at the dose of 500 mg/day for 3 days. Mono- and/or polyclonal antibodies could be used as therapy for corticosteroid-resistant AR. First-line antibody therapy will be permitted only if biopsy indicate a severe vascular rejection (Banff IIB or III).
Prophylactic treatment:
Prophylactic antiviral treatment with oral ganciclovir 450 mg/day, and PCP prevention with 400 mg Sulfamethoxazole and 80 mg of Trimethoprim/day will be given to all patients on days 1-90.
Endpoints.
The primary endpoint:
- adherence to the Tacrolimus administration defined as self-reported number of missed drug ingestions scored in Morisky Medical Adherence Assessment questionnaire
Secondary endpoints:
- efficacy failure defined as biopsy proven rejection, renal function, incidence of adverse events (AEs) and graft loss or death at the end of the analysis period
Statistical analysis The data collected will be analyzed with Fisher's exact test, Wilcoxon' matched pair test and Kaplan-Meier's test
- Conditions
- Medication Adherence
- Being tested
- Tacrolimus BID, Advagraf QD
- Keywords
- non adherence, Tacrolimus, Advagraf
- Medical subject headings
- Medication Adherence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus BIDDrug
Also called Prograf, Tacrocell
Administration of Tacrolimus BID
Advagraf QDDrug
Also called Advagraf
administration of Advagraf QD
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus BID | Active comparator | 20 patients receiving twice daily (BID) Tacrolimus Receives: Drug: Tacrolimus BID |
| Advagraf QD | Active comparator | 40 patients randomized to receive once daily (QD) Advagraf Receives: Drug: Advagraf QD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morisky Medical Adherence Assessment questionnaire
adherence to the Tacrolimus QD administration defined as self-reported number 9on scale from 1-8) of missed drug ingestions scored in Morisky Medical Adherence Assessment questionnaire
Measured: 2 years
Secondary outcomes (3)
graft and patient survival
% of patients and grafts alive after 1st and 2nd year of study
Measured: 2 years
gfr
gfr - glomerular filtration rate - a measure of renal function, in ml/min/1.73m2
Measured: 2 years
adverse events
percentage of patients with complications
Measured: 2years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2016 (estimated)
- Study startAug 2016
- Primary completionAug 2018 (estimated)
- Study completionAug 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Medication AdherenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc, Teva Pharma
- Responsible party
- Principal investigator, Alexander yussim, Rabin Medical Center
- Investigators
- Eyan Mor, MD, Study director, Rabin Med CTR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02805842
- Sponsor's protocol ID
- 0076-16 RMC
- Acronym
- Advagraf
- Status last verified
- Jul 2016
- First submitted
- 8 May 2016
- Last updated
- 12 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 12;9(9):CD012854. doi: 10.1002/14651858.CD012854.pub2.
PubMed 36094829
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Incidence of Non Adherence to Treatment With Once-daily Formulation of Tacrolimus (ADVAGRAF) in Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT02805842
- Acronym / sponsor ID
- Advagraf / 0076-16 RMC
- Conditions
- Medication Adherence
- Keywords
- non adherence, Tacrolimus, Advagraf
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc, Teva Pharma
- Study start
- Aug 2016
- Primary completion
- Aug 2018 (estimated)
- Study completion
- Aug 2018 (estimated)
- First posted
- 20 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aim The primary objective of this study is to compare medication adherence with medical therapy in patients receiving once-daily versus twice-daily tacrolimus regimens.
Participants 60 adult renal transplant patients randomized 1:2 into twice-daily and once-daily tacrolimus groups
Outcomes The primary outcome will be medication adherence to the once-daily and twice-daily regimens, measured in terms of implementation. Secondary outcomes will include graft and patient survival, renal function and adverse events. Follow up - 12 months
Detailed description
Following randomization (Day 0), 60 kidney transplant recipients of deceased or live kidneys will be randomized 1:2 into control and study- experimental arm. In control arm, named Tacrolimus BID arm, tacrolimus will be administered unchanged twice daily, morning and evening, while in study--experimental group named Tacrolimus QD- Advagraf, the Advagraf tacrolimus formulation will be administered once daily in the morning. In both groups doses will be adjusted to maintain tacrolimus trough levels at 10-12 ng/mL (days 1-28), 8-10 ng/mL (days 29-168) and 6-8 ng/mL thereafter for both treatment arms.
Adjunct immunosuppression. Per-protocol rejection prophylaxis: All patients will receive Basiliximab induction at 20mg/bw on days 0 and 4. Methylprednisolone will be administered as intravenous bolus doses of 500 mg , 250 mg and 125 mg perioperatively, on days 0,1 and 2. Thereafter oral prednisone will be given: 20 mg/day (days 2-14), 15 mg/day (days 15-30), 10 mg/day (days 30-45), 7.5 mg/day (days 45-60) and 5 mg/day thereafter. MMF (2 g BID) will be started preoperatively, and reduced to 500 mg three times daily after 14-30 days.
Rejection treatment: First-line acute rejection (AR) therapy with corticosteroids will be administered at the dose of 500 mg/day for 3 days. Mono- and/or polyclonal antibodies could be used as therapy for corticosteroid-resistant AR. First-line antibody therapy will be permitted only if biopsy indicate a severe vascular rejection (Banff IIB or III).
Prophylactic treatment:
Prophylactic antiviral treatment with oral ganciclovir 450 mg/day, and PCP prevention with 400 mg Sulfamethoxazole and 80 mg of Trimethoprim/day will be given to all patients on days 1-90.
Endpoints.
The primary endpoint:
- adherence to the Tacrolimus administration defined as self-reported number of missed drug ingestions scored in Morisky Medical Adherence Assessment questionnaire
Secondary endpoints:
- efficacy failure defined as biopsy proven rejection, renal function, incidence of adverse events (AEs) and graft loss or death at the end of the analysis period
Statistical analysis The data collected will be analyzed with Fisher's exact test, Wilcoxon' matched pair test and Kaplan-Meier's test
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus BID | Active comparator | Drug: Tacrolimus BID20 patients receiving twice daily (BID) Tacrolimus |
| Advagraf QD | Active comparator | Drug: Advagraf QD40 patients randomized to receive once daily (QD) Advagraf |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age: 18 Years to 60 Years
- Gender: both
- Patients willing and able to participate in this study
- Patients who signed the informed consent form
- Patients who can visit the center based on the study schedule in the protocol
Key exclusion criteria (10 listed)
- Patients who had previously received a kidney or another organ
- Patients, having positive lymphocyte cross-match
- Patients with PRA >50%
- Patients, who underwent desensitization
- Patients, who were diagnosed with cancer in the last five years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tacrolimus BIDAlso: Prograf, TacrocellAdministration of Tacrolimus BID | Drug | Tacrolimus BID |
| Advagraf QDAlso: Advagrafadministration of Advagraf QD | Drug | Advagraf QD |
Primary outcome
Morisky Medical Adherence Assessment questionnaire
Time frame: 2 years
adherence to the Tacrolimus QD administration defined as self-reported number 9on scale from 1-8) of missed drug ingestions scored in Morisky Medical Adherence Assessment questionnaire
3 secondary outcomes
graft and patient survival
Time frame: 2 years
gfr
Time frame: 2 years
adverse events
Time frame: 2years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2016.
- Derived from this study: PubMed 36094829Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 12;9(9):CD012854. doi: 10.1002/14651858.CD012854.pub2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eyan Mor, MD study director
Rabin Med CTR
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tacrolimus BID and Advagraf QD in people with Medication Adherence, run by Rabin Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eytan Mor, MD (97239376472, emor@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Morisky Medical Adherence Assessment questionnaire (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02805842, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2016.