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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 16 December 2017
Main ID:  NCT00279708
Date of registration: 18/01/2006
Prospective Registration: Yes
Primary sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Public title: Atorvastatin to Treat Pulmonary Sarcoidosis
Scientific title: Atorvastatin as a Disease Modifying Agent in Stage II and III Pulmonary Sarcoidosis: A Randomized, Double-Blind, Placebo-Controlled Trial
Date of first enrolment: January 2006
Target sample size: 55
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT00279708
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).  
Phase:  Phase 2
Countries of recruitment
United States
Contacts
Name:     Joseph R Fontana, M.D.
Address: 
Telephone:
Email:
Affiliation:  National Heart, Lung, and Blood Institute (NHLBI)
Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

Patients are eligible for the trial if they are 18-70 years old with radiographic stages II
and III pulmonary sarcoidosis, and are on prednisone, methotrexate, or azathioprine for
pulmonary sarcoidosis or who are steroid-requiring. Patients with extra-pulmonary
sarcoidosis (except cardiac and neurosarcoidosis) may be eligible as long as they have
active pulmonary (stage II or III) sarcoidosis.

Steroid-Requiring History:

A steroid-requiring patient is one who was previously stable but who ultimately experiences
(a) increased symptoms associated with radiographic deterioration, and/or, (b) met the
criteria for relapse and/or functional deterioration. In addition, patients who were
prescribed prednisone for sarcoidosis, but have self-discontinued it (yet still have
clinical and symptomatic disease and/or evidence of pulmonary functional deterioration)
will be considered steroid-requiring.

This latter group of steroid-requiring patients is eligible for enrollment if they are
willing to resume taking their latest stabilizing dose of prednisone for at least four
weeks prior to study entry. If their dose cannot be determined, then 40 mg will be used.

Therefore, a history of symptomatic or clinical deterioration leading to therapy
initiation, or a history of decline associated with attempts to decrease therapy should be
established. Medical records review and discussion with the prescribing physician will be
used to establish this history.

Radiographic Stages of Pulmonary Sarcoidosis:

STAGE< TAB> DESCRIPTION

0< TAB> Normal Chest Radiograph

I< TAB> Bilateral Hilar Lymphadenopathy

II< TAB> Pulmonary Infiltration and Bilateral Hilar Lymphadenopathy

III< TAB> Pulmonary Infiltration alone

Steroid-requiring refers to one of three situations:

Patients who meet relapse criteria or functional deterioration.

Functional deterioration criteria that warrants prednisone therapy includes:

If VC fell to 75% of the best recorded value for the patient before any treatment

If VC fell to greater than 50% of predicted value

IF DLCO fell to less than 60% of the best recorded value prior to their treatment

Patients who are on a previously prescribed systemic steroid, or alternative agent such as
methotrexate or azathioprine, primarily for pulmonary sarcoidosis. Alternative agents must
first be changed to roughly equivalent anti-inflammatory dose of prednisone and the patient
should be stable on this dose for at least four weeks prior to randomization.

Patients who have substantial respiratory symptoms (distressing cough or dyspnea, which
interferes with daily activities that would warrant therapy as per the standard of practice
in the US.

Extra Pulmonary Sarcoidosis:

Patients with extra pulmonary sarcoidosis (except neurosarcoidosis and cardiac sarcoidosis)
may be eligible as long as they have active pulmonary (stage II or III) sarcoidosis. All
patients will be referred to an NIH ophthalmologist. Steroid therapy may be modified based
upon the recommendations of the consultants, as well as per the lapse criteria described
above.

EXCLUSION CRITERIA:

- Moderate to severe pulmonary fibrosis (stage IV sarcoidosis greater than 50% fibrosis)

- Lung Disease such as asthma, COPD, ILD (other than sarcoid-related)

- History of significant beryllium or asbestos exposure

- Pregnancy; or Active lactation/ child-bearing age female without appropriate birth
control methods

- HIV disease

- Hepatitis C and Active Hepatitis B

- Other intervention protocols

- Immunosuppressive therapy (systemic or inhaled) other than corticosteroids or
methotrexate

- Significant cardiac disease (NYSHA class greater than III), or serious coronary
disease (unstable angina)

- Use of statins within 12 weeks of enrollment

- Allergies or intolerance to statins

- Liver disease (transaminases greater than 1.5X upper limits of normal) or cirrhosis

- Bleeding diathesis that is not correctable

- Inability to perform CPET (cycle ergometer) or PFT maneuvers

- Inability to understand the risks of the trial and the inability to complete the
questionnaire

- Malignancy-- requiring chemotherapy or radiation therapy; except certain types of skin
cancer that have been excised and have not spread.

- Myopathy, diagnosed via muscle biopsy (other than sarcoid-related myopathy); CPK
grater than 1.5 upper limits of normal

- Surgical Risk Category [American Society of Anesthesiologists (ASA) class IV

- Ingestion of grapefruit juice or certain herbal preparations (see below), or
medications that are potent inhibitors or inducers of the CYP3A4 system (see section
12.4 under precautions)

- Alcohol abuse (greater than 4 drinks/day)

- Bleeding into the brain or parts of the eyes (retina) (within the past year prior to
enrollment)

- Uncontrolled Hypertension (SBP greater than 185 or DBP greater than 100 on two or more
visits or assessments)

- Uncontrolled Diabetes Mellitus (Serum glucose level on two or more tests per day
greater than 250 mg/dl or erratic blood sugar levels, noted on at least 2 or more
assessments; and/or HgbA1C greater than 2x the upper limits of normal).

- Neurosarcoidosis

- Sarcoid Uveitis (Posterior Uveitis) or any Uveitis that cannot be managed with topical
steroids alone, as determined by an ophthalmologist

- (Clinically apparent) Cardiac Sarcoidosis

- Active Smoker (Smoked within the past 2 months prior to randomization)

- Sickle cell disease (SS, SC, and sickle cell-beta thalassemia)

- Aseptic necrosis of the hip joints

Patients taking the following preparations will not be allowed to participate in the study
unless they agree to discontinue usage at least two weeks prior to randomization and for
the duration of the study period: grapefruit juice and herbal remedies that may lead to
severe liver injury and/or muscle injury if taken with atorvastatin, including: Skullcap,
chaparral, Germander, Jin Bu Huan, Valerian, Comfrey, and Eucalyptus. Since other products
such as St. John s Wort, oat bran, and pectin can reduce the effectiveness of atorvastatin,
they and similar agents, should also be discontinued at least two weeks before
randomization and for the duration of the study period.

Subjects with inactive hepatitis B will require antiviral prophylaxis with an agent such as
lamivudine, while on prednisone therapy.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All
Health Condition(s) or Problem(s) studied
Sarcoidosis, Pulmonary
Intervention(s)
Drug: Atorvastatin
Other: Placebo Oral Tablet
Primary Outcome(s)
The Steroid Sparing Period [Time Frame: 1 year]
Secondary Outcome(s)
Exercise Performance [Time Frame: 12 month treatment period]
Pulmonary Function Tests [Time Frame: 12 month treatment period]
Pulmonary Sarcoidosis Flares [Time Frame: 1 year]
Quality of Life and Dyspnea Scales [Time Frame: 12 month treatment period]
Secondary ID(s)
06-H-0072
060072
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available: Yes
Date Posted: 12/08/2016
Date Completed:
URL: https://clinicaltrials.gov/ct2/show/results/NCT00279708
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