Phase 3
Completed N=89
Efficacy and Safety of Sirolimus in LAM
Source: ClinicalTrials.gov NCT00414648 ↗Enrolled (actual)
89
Serious AEs
46.1%
Results posted
Nov 2023
Primary outcomePrimary: Changes in Forced Expiratory Volume in One-second (FEV1) Slope in Milliliters Per Month — 1; -12 milliliters per month — p=<0.001
◆ Published Evidence
Highly cited
1,116citations · ~74 / year
Efficacy and safety of sirolimus in lymphangioleiomyomatosis.
Summary
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that is caused by genetic mutations. It results in the uncontrolled growth of an unusual type of smooth muscle cell in the lung. These cells invade lung tissue, including the airways, blood vessels, and lymph vessels, and restrict the flow of air, blood, and lymph, respectively. Respiratory failure, lung collapse (pneumothorax), and pleural effusions (chylothorax) are hallmarks of the disease. This study will evaluate the safety and effectiveness of sirolimus, an inhibitor of the mTOR pathway, in stabilizing or improving lung function in people with LAM.
Linked Publications (5)
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Efficacy and safety of sirolimus in lymphangioleiomyomatosis.
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Serum VEGF-D a concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial.
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Analysis of the MILES cohort reveals determinants of disease progression and treatment response in lymphangioleiomyomatosis.
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A Novel Quantitative Computed Tomographic Analysis Suggests How Sirolimus Stabilizes Progressive Air Trapping in Lymphangioleiomyomatosis.
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Cyst-based measurements for assessing lymphangioleiomyomatosis in computed tomography.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Changes in Forced Expiratory Volume in One-second (FEV1) Slope in Milliliters Per Month |
1; -12 | <0.001 sig |
| SECONDARY Percent of Participants With Serious Adverse Events |
50; 41.86 | .441 |
| SECONDARY Changes in FVC Slope in ml/Month |
8; -11 | 0.001 sig |
| SECONDARY Rate of Change in Diffusing Capacity for Carbon Monoxide (DLCO) in ml/Min/mmHg |
-0.01; -0.06 | 0.17 |
| SECONDARY Rate of Change in Total Lung Volume in ml Per Month |
8; -2 | 0.34 |
| SECONDARY Rate of Change in Six Minute Walk Distance in Meters/Month |
1.65; 1.47 | 0.88 |
| SECONDARY Rate of Change in Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels in pg/ml Per Month |
-88.01; -2.42 | 0.001 sig |
Eligibility Criteria
Inclusion Criteria
- Age 18 or older
- Signed and dated informed consent
- Diagnosis of LAM based on compatible chest CT scan and a) biopsy or cytology consistent with LAM, or b) presence of tuberous sclerosis, angiomyolipoma or chylous pleural effusion; or c) a VEGF-D level of at least 800 pg/ml
- Forced expiratory volume in one second (FEV1) of 70% or less of predicted value after administration of a bronchodilator
Exclusion Criteria
- Known allergy to sirolimus
- History of heart attack, angina, or stroke due to clogging, narrowing, and hardening of the arteries and blood vessels
- Significant hematologic or hepatic abnormality (transaminase levels greater than three times the upper limit of normal, HCT less than 30%, platelets less than 80,000/cubic mm, adjusted absolute neutrophil count less than 1,000/cubic mm, total white blood cell count less than 3,000/cubic mm)
- Intercurrent infection at the time treatment with sirolimus begins
- Any surgery involving entry into a body cavity or requiring three or more sutures within 8 weeks of initiation of study drug
- Use of an investigational drug within the 30 days prior to random assignment
- Uncontrolled hyperlipidemia
- Previous lung transplant or currently on lung transplant list
- Unable to attend scheduled study visits
- Unable to perform pulmonary function tests
- Creatinine levels greater than 2.5 mg/dl
- Chylous ascites severe enough to affect diaphragmatic function
- Pleural effusion severe enough to affect pulmonary function, as determined by the study physician
- History of acute pneumothorax within the 2 months prior to study entry
- History of malignancy within the 2 years prior to study entry (except for squamous or basal cell skin cancer)
- Use of estrogen containing medication within the thirty days prior to randomization
- Unable or unwilling to use adequate contraception
- Pregnant, breastfeeding, or plans to become pregnant within the next 2 years
Data sourced from ClinicalTrials.gov (NCT00414648) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.