FK506 (Tacrolimus) in Pulmonary Arterial Hypertension

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01647945
• Date of registration: 18/07/2012
• Prospective Registration: No
• Primary sponsor: Edda Spiekerkoetter
• Public title: FK506 (Tacrolimus) in Pulmonary Arterial Hypertension TransformPAH
• Scientific title: Single-Center Randomized Controlled Phase II Study of Safety and Efficacy of FK-506 (Tacrolimus) in Pulmonary Arterial Hypertension
• Date of first enrolment: July 2012
• Target sample size: 23
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01647945
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Roham Zamanian, MD
• Affiliation: Stanford University

• Name: Edda Spiekerkoetter, MD
• Affiliation: Stanford University

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age = 18 and < 70 years

2. Diagnosis of WHO Group I Pulmonary Arterial Hypertension (PAH) (Idiopathic (I)PAH,
Heritable PAH (including Hereditary Hemorrhagic Telangiectasia), Associated (A)PAH
(including collagen vascular disorders, drugs+toxins exposure, congenital heart
disease, and portopulmonary disease).

3. Stable on active PAH treatment including any prostacycline or phosphodiesterase
inhibitors and the endothelin antagonist Ambrisentan alone or in combination
(stability defined as: <10% change in 6MWD, no change in NYHA class, no
hospitalization or addition of PAH therapy for at least 3 months).

4. Previous Right Heart Catheterization that documented:

1. Mean PAP = 25 mmHg.

2. Pulmonary capillary wedge pressure < 15 mmHg.

3. Pulmonary Vascular Resistance = 3.0 Wood units or 240 dynes/sec/cm5

5. WHO functional class I to IV as judged by the investigator.

Exclusion Criteria:

1. WHO Group II - V Pulmonary Hypertension.

2. Current or prior experimental PAH treatments within the last 6 months (including but
not limited to tyrosine kinase inhibitors, rho-kinase inhibitors, or cGMP modulators).

3. Current active treatment with the dual endothelin receptor antagonist bosentan.

4. TLC < 60% predicted; if TLC b/w 60 and 70% predicted, high resolution computed
tomography must be available to exclude significant interstitial lung disease.

5. FEV1 / FVC < 70% predicted and FEV1 < 60% predicted

6. Significant left-sided heart disease (based on screening Echocardiogram):

1. Significant aortic or mitral valve disease

2. Diastolic dysfunction = Grade II

3. LV systolic function < 45%

4. Pericardial constriction

5. Restrictive cardiomyopathy

6. Significant coronary disease with demonstrable ischemia.

7. Chronic renal insufficiency defined as an estimated creatinine clearance < 30 ml/min
(by MDRD equation).

8. Current atrial arrhythmias not under optimal control.

9. Uncontrolled systemic hypertension: SBP > 160 mm or DBP > 100mm

10. Severe hypotension: SBP < 80 mmHg.

11. Pregnant or breast-feeding.

12. Psychiatric, addictive, or other disorder that compromises patient's ability to
provide informed consent, follow study protocol, and adhere to treatment instructions.

13. Active cyclosporine use.

14. Known allergy or hypersensitivity to FK-506.

15. Planned initiation of cardiac or pulmonary rehabilitation during period of study.

16. Human Immunodeficiency Virus infection.

17. Moderate to severe hepatic dysfunction with a Pugh score >10.

18. Hyperkalemia defined as Potassium > 5.1 mEq/L at screening .

19. Known active infection requiring antibiotic, antifungal, or antiviral therapies.

20. Co-morbid conditions that would impair a patient's exercise performance and ability to
assess WHO functional class, including but not limited to chronic low-back pain or
peripheral musculoskeletal problems.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: FK506 level 2-3 ng/ml

Drug: FK506 level < 2 ng/ml

Drug: FK506 level 3-5 ng/ml

Drug: Placebo

Primary Outcome(s)

Safety of Low-dose FK-506 in PAH [Time Frame: 18 weeks]

Secondary Outcome(s)

Efficacy of Low-dose FK-506 in Pulmonary Arterial Hypertension (PAH) Measured by Change in 6-min Walk Distance (6MWD) [Time Frame: baseline to 16 weeks]

Number of Combined Clinical Events [Time Frame: Baseline to 16 weeks]

Secondary ID(s)

PAH-70522

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Stanford University

Results

• Results available: Yes
• Date Posted: 05/10/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01647945