Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02608606
Other study ID # FKoral-sl
Secondary ID
Status Completed
Phase N/A
First received November 3, 2015
Last updated October 10, 2016
Start date March 2015
Est. completion date March 2016

Study information

Verified date October 2016
Source Pontificia Universidad Catolica de Chile
Contact n/a
Is FDA regulated No
Health authority Chile: Comité de Ética Científico
Study type Interventional

Clinical Trial Summary

After liver transplantation one of the most important cost, for both patients and their health insurance system, is immunosuppressive drug therapy. Tacrolimus (FK 506) is considered the cornerstone of immunosuppressive therapy in solid organ transplantation. Oral administration is the usual route, however, sublingual (SL) administration has been recently reported. This method of administration avoids first pass metabolism and allows an alternative route after transplant surgery, particularly in those patients who should extend the period of fasting (prolonged intubation, ileus, etc). Interestingly, in some studies, the dose of tacrolimus SL required to maintain similar plasma concentrations compared with oral administration, is significantly lower, even up to 50%, which can result in considerable savings in short and long term. Among these studies, only one was conducted in liver recipients. This study suggest that SL administration of tacrolimus could allow to obtain similar concentrations compared with oral administration. The design of this study did not assess the existence of differences in the dose required and only included six patients.


Description:

The patient will be scheduled fasting to liver transplant unit where the pharmacokinetic study was performed. After installation of the venous needle, blood samples will be collected on 4 ml tubes with EDTA as an anticoagulant at the following intervals of time in hours: 0 (immediately before the oral administration of tacrolimus); 0.5; 1.0; 1.5; 2; 4; 6; 9 and 12 h. post-dose. Once the blood samples taken, the tubes will be plugged, invest gently to mix with anticoagulant and stored at -20 ° C until analysis.

Subsequently, tacrolimus administration was change to sublingual route and dose was adjusted to obtain similar trough levels to those determined on per oral administration. The capsule be opened and its contents shall be deposited in the sublingual mucosa. To be ensure that drug will be absorted the patient will be instructed to insistently that after sublingual placement of the drug, should not swallow the capsule content for at least 15 minutes. The same pharmacokinetic study described for the oral route will be performed.

Breakfast will be administered 2 hours after ingesting the drug and lunch and dinner 6 and 10 hours after respectively. Fluid intake is discretionary.


Recruitment information / eligibility

Status Completed
Enrollment 20
Est. completion date March 2016
Est. primary completion date March 2016
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria:

- Outline of immunosuppression that includes tacrolimus dosing every 12 hours.

- Stable plasma levels of tacrolimus in 3 consecutive measurements.

- Stable blood tests: biochemical profile, creatinine and liver profile.

- Absence of treatment with drugs that have interaction with tacrolimus (antifungal and diltiazem) and use of grapefruit juice.

- Absence of active bacterial or viral infection and rejection episodes within 8 weeks prior.

Exclusion Criteria:

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms

  • Effects of Immunosuppressant Therapy
  • Evidence of Liver Transplantation

Intervention

Drug:
Tacrolimus
compared oral administration versus sublingual administration of tacrolimus.

Locations

Country Name City State
Chile Pontificia Universidad Catolica de Chile Santiago

Sponsors (1)

Lead Sponsor Collaborator
Pontificia Universidad Catolica de Chile

Country where clinical trial is conducted

Chile, 

References & Publications (11)

Agopian VG, Petrowsky H, Kaldas FM, Zarrinpar A, Farmer DG, Yersiz H, Holt C, Harlander-Locke M, Hong JC, Rana AR, Venick R, McDiarmid SV, Goldstein LI, Durazo F, Saab S, Han S, Xia V, Hiatt JR, Busuttil RW. The evolution of liver transplantation during 3 — View Citation

Collin C, Boussaud V, Lefeuvre S, Amrein C, Glouzman AS, Havard L, Billaud EM, Guillemain R. Sublingual tacrolimus as an alternative to intravenous route in patients with thoracic transplant: a retrospective study. Transplant Proc. 2010 Dec;42(10):4331-7. — View Citation

Nasiri-Toosi Z, Dashti-Khavidaki S, Nasiri-Toosi M, Khalili H, Jafarian A, Irajian H, Abdollahi A, Sadrai S. Clinical pharmacokinetics of oral versus sublingual administration of tacrolimus in adult liver transplant recipients. Exp Clin Transplant. 2012 D — View Citation

Rabkin JM, Corless CL, Rosen HR, Olyaei AJ. Pharmacoeconomic study of tacrolimus-based versus cyclosporine-based immunosuppressive therapy following liver transplantation. Transplant Proc. 2001 Feb-Mar;33(1-2):1532-4. — View Citation

Reams BD, Palmer SM. Sublingual tacrolimus for immunosuppression in lung transplantation: a potentially important therapeutic option in cystic fibrosis. Am J Respir Med. 2002;1(2):91-8. Review. — View Citation

Reams D, Rea J, Davis D, Palmer S. Utility of sublingual tacrolimus in cystic fibrosis patients after lung transplantation. J Heart Lung Transplant. 2001 Feb;20(2):207-208. — View Citation

Romero I, Jiménez C, Gil F, Escuin F, Ramirez E, Fudio S, Borobia A, Carcas A. Sublingual administration of tacrolimus in a renal transplant patient. J Clin Pharm Ther. 2008 Feb;33(1):87-9. doi: 10.1111/j.1365-2710.2008.00884.x. — View Citation

Srinarong P, Pham BT, Holen M, van der Plas A, Schellekens RC, Hinrichs WL, Frijlink HW. Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administration. Drug Dev Ind Pharm. 2012 Apr;38(4):490-500. doi: 10.3 — View Citation

Tsapepas D, Saal S, Benkert S, Levine D, Delfin M, Cremers S, Amann S, Dadhania D, Kapur S, Aull M. Sublingual tacrolimus: a pharmacokinetic evaluation pilot study. Pharmacotherapy. 2013 Jan;33(1):31-7. doi: 10.1002/phar.1149. — View Citation

van de Plas A, Dackus J, Christiaans MH, Stolk LM, van Hooff JP, Neef C. A pilot study on sublingual administration of tacrolimus. Transpl Int. 2009 Mar;22(3):358-9. doi: 10.1111/j.1432-2277.2008.00779.x. Epub 2008 Oct 30. — View Citation

Watkins KD, Boettger RF, Hanger KM, Leard LE, Golden JA, Hoopes CW, Singer JP. Use of sublingual tacrolimus in lung transplant recipients. J Heart Lung Transplant. 2012 Feb;31(2):127-32. doi: 10.1016/j.healun.2011.10.015. Epub 2011 Dec 16. — View Citation

* Note: There are 11 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Compare tacrolimus exposure using per oral and sublingual administration employing AUC (Area Under the Curve). compared oral administration versus sublingual administration of tacrolimus 30 days Yes
Secondary Compare tacrolimus dose necessary to obtain similar trough levels employing per oral and sublingual administration compared oral administration versus sublingual administration of tacrolimus 30 days Yes
See also
  Status Clinical Trial Phase
Recruiting NCT02239991 - Management of Perioperative Coagulopathy With Thromboelastometry (ROTEM) in Liver Transplant N/A
Recruiting NCT03013634 - Protective Effects of Dexmedetomidine on Myocardial Injury During Liver Transplantation N/A
Active, not recruiting NCT02579408 - Quantifying Steatosis in Liver Transplant Donors
Completed NCT02008097 - Clinical Benefits of B-Flow Ultrasound N/A
Completed NCT04763096 - Evaluate the Efficacy and Safety of the ADVAGRAF® Phase 4
Recruiting NCT01607788 - Prospective Liver Tumor (ProLiT) Database N/A
Recruiting NCT01766518 - The Study to Evaluate Efficacy and Safety of MY-REPT Capsule in Primary, Liver Transplantation Recipients (MYLT1) Phase 4
Not yet recruiting NCT01860716 - Impact of Melatonin in the Pretreatment of Organ Donor and the Influence in the Evolution of Liver Transplant. Phase 3
Completed NCT01022476 - Raltegravir in Patients With End Stage Liver Disease and in Transplant Recipients Phase 1/Phase 2
Completed NCT01546064 - Study to Establish Whether the Use of T-Tube in Bile Duct Anastomosis in Liver Transplantation Decreases Morbidity N/A
Completed NCT02263703 - Immunogenicity of HPV Vaccine in Immunosuppressed Children Phase 3
Terminated NCT00473824 - Randomized Phase II Study of Hepatitis C Immune Globulin Intravenous (Human), Civacir(TM), in Liver Transplantation Phase 2
Terminated NCT00151632 - Reduction of Tacrolimus Dose in Association With Mycophenolate Mofetil After Liver Transplantation Phase 3
Active, not recruiting NCT02350218 - Safety, Efficacy of Eglandin® in Living Donor Liver Transplanted Patient (PROVISION) Phase 2
Recruiting NCT02451046 - Usefulness of Alpha-GST in Liver Transplantation N/A
Completed NCT00177931 - Cefepime Pharmacokinetics in Liver Transplant Recipients in an Intensive Care Unit N/A
Completed NCT01147380 - Safety Study of Liver Natural Killer Cell Therapy for Hepatoma Liver Transplantation Phase 1
Terminated NCT00694408 - A Pilot Trial of Pediatric Liver Transplantation Without Steroids Phase 3
Terminated NCT00375895 - Switch From Tacrolimus to Cyclosporin in the Treatment of Recurrent Hepatitis C After Liver Transplantation Phase 3
Recruiting NCT01157403 - Autologous Transplantation of Mesenchymal Stem Cells for Treatment of Patients With Onset of Type 1 Diabetes Phase 2/Phase 3