The MILES Trial
MILES Trial Reports Additional Risk for Sirolimus
The safety of study participants in the MILES Trial is of the utmost concern to the MILES Trial Study Team. We would like to inform study participants of a potential risk which has been identified for participation in the MILES Trial.
There is the risk that sirolimus treatment can be associated with inflammation or build up of fluid in the sac around the heart. These conditions are known as pericarditis or pericardial effusion, respectively. Fluid around the heart can cause low blood pressure which can result in damage to organs such as the kidney or even death. Pericardial fluid might need to be drained emergently by an intervention called pericardiocentesis or a surgical procedure.
Pericarditis or pericardial effusion occurred in 2% (82) of 4068 patients in clinical trials of transplant patients treated with sirolimus. It has also occurred in one participant in the MILES Trial. If you develop this condition, the study article may be stopped.
MILES Trial participants will be offered the chance to review a new informed consent at their next study visit. The revised consent will include this new risk of study participation. Currently enrolled participants may decide if they wish to continue their participation or withdraw from the study.
If you have any questions, please contact the MILES Trial Study Team. Complete contact information is listed below.
*If you are interested in receiving more information about the trial, you may email milestrial@cchmc.org or contact the MILES Trial Project Manager, Leslie Korbee at 513.636.6272 or MILES Trial Lead Study Coordinator Susan McMahan, RN at 513.636.6215. We welcome your call or email.
You may also contact MILES Trial Study staff at any of the MILES Trial sites which are listed below:
US Sites
Cincinnati Children's Hospital Medical Center - Cincinnati, OH
Principal Investigator: Frank McCormack, MD
Contact Person: Leslie Korbee
Office: 513.636.6272
Email: MILEStrial@cchmc.org
Medical University of South Carolina - Charleston, SC
Principal Investigator: Charlie Strange, MD
Contact Person: Amie Gitter, RN
Office: 843.792.6569
Email: gitterac@musc.edu
Oregon Health and Science University - Portland, OR
Principal Investigator: Alan Barker, MD
Contact Person: Kathy Bacon
Office: 503.494. 6949
Email: baconka@ohsu.edu
Cleveland Clinic - Cleveland, OH
Principal Investigator: Jeffrey Chapman, MD
Contact Person: Diane Faile
Office: 216.444.9975
Email: failed@ccf.org
National Jewish Medical & Research Center - Denver, CO
Principal Investigator: Kevin Brown, MD
Contact Person: Marianne Morrison
Office: 303.270.2053
Email: morrisonm@njc.or
University of Florida at Gainesville - Gainesville, FL
Principal Investigator: Mark Brantly, MD
Contact Person: Pamela Schreck, MSN
Office: 352.294.0512
Email: pschreck@ufl.edu
National Institutes of Health - Bethesda, MD
Principal Investigator: Joel Moss, MD, PhD
Contact Person: Mary Haughey, RN
Office: 301.496.3632
Email: mhaughey@nhlbi.nih.gov
UCLA - Los Angeles, CA
Principal Investigator: Joseph P. Lynch, MD
Contact Person: Eileen Callahan,
Office: 310.794.2466
Email: ecallahan@mednet.ucla.edu
University of Texas Health Science Center at Tyler- Tyler, TX
Principal Investigator: James Stocks, MD
Contact Person: Janice Hoeft, RN
Office: 903.877.5518
Email: Janice.hoeft@uthct.edu
Brigham and Women's Hospital - Boston, MA
Principal Investigator: Hilary J. Goldberg, MD
Contact Person: Elizabeth Peters, BSN, RN
Office: 617.525.9331
Email: epeters2@partners.org
Canadian Site
University of Toronto, Toronto General Hospital - Toronto, Canada
Principal Investigator: Lianne Singer, MD
Contact Person: Mihaiela Sichitiu
Office: 416.340.4800 ext. 2021
Email: msichiti@uhnres.utoronto.ca
Japanese Sites
Niigata - Niigata University Medical & Dental Hospital
Principal Investigator: Koh Nakata, MD, PhD
Contact Person: Chinatsu Kaneko
Phone: +81 (25) 227.2022
Email: kanekochinatsu@bmrc.jp
Osaka - NHO Kinki-Chuo Chest Medical Center
Principal Investigator: Yoshikazu Inoue, MD, PhD
Contact Person: Kazuhiro Hirohata
Phone: +81 (72) 252.1313
Email: crc@kch.hosp.go.jp
MILES Trial Description
The MILES Trial is conducted through the Rare Lung Diseases Consortium - a network of Universities funded by the National Institutes of Health (NIH) to perform cooperative trials. The Trial will be placebo-controlled, meaning some patients will get a ‘sugar pill'; randomized, meaning that the process of assigning patients to placebo or the drug sirolimus (rapamycin) therapy is based on chance, such as the flipping of a coin; and double-blind, meaning that neither the patient or the doctor will know who is getting what. This is a tried and true design which eliminates biases. We are hoping to enroll 60 patients each in the placebo and treatment groups. Patients who receive rapamycin will take the intermediate dose used in the first Cincinnati trial (2mg), comparable to the dose that is generally used in kidney transplant patients. We will measure pulmonary function tests, six-minute walk distance, and quality of life and dyspnea (shortness of breath) scores by questionnaire. To qualify, patients must be able to give informed consent, have abnormal lung function (FEV1<70%) and be free from pleural effusion (fluid in the chest cavity) of a size that is sufficient to influence lung function. Kidney tumor size will not be followed. The trial will be three years long, but we will take "peeks' at an interim time point. If lung function (FEV1) is significantly better in the rapamycin group at the interim analysis, all patients will be crossed over from the placebo group to receive the drug and the trial will continue to monitor safety and efficacy to the two-year point. The intent of this design is to be able to detect a robust effect of the drug early and a more subtle effect late (two-year point). The side effects that we will be monitoring include susceptibility to infection, mouth ulcers, elevated cholesterol and an unusual form of pneumonia-like lung inflammation that is not due to infection.
Click here to view The MILES Trial Brochure.
Why a Placebo?
The answer is that we will have only one opportunity to answer the question of whether sirolimus (also known as rapamycin) is an effective therapy for LAM. If we don't do this correctly, a lot of people may be harmed. Perhaps the best way to illustrate this point is to review how we as investigators and physicians have failed patients in finding therapies for another scarring lung disease, idiopathic pulmonary fibrosis (IPF). In IPF, the lung becomes progressively stiffer and more shrunken over time as scar replaces the tiny air sacs that take up oxygen. The disease is relentlessly progressive, and usually fatal, often within two years of presenting with shortness of breath. Treatment with high doses of prednisone and chemotherapy agents were accepted as the standard of care for decades without any proof; a proper trial was never performed. Over time, it became clear to almost all physicians who manage IPF patients that this toxic therapy, which was often complicated by serious infections, osteoporosis, cataracts, hip and spine fractures, is usually ineffective. A lot of patients were hurt. A few years ago, an investigator in Europe reported very encouraging results with a new drug from a small pilot, much like the rapamycin trial we performed in Cincinnati. Patients with IPF who received the drug interferon gamma had improved lung function. There were testimonials from patients and physicians about the miraculous benefits of the drug, including reports that the need for oxygen vanished and patients were again able to exercise, etc. Although the drug was FDA-approved for another indication, and many physicians began prescribing it for IPF ‘off label' at tremendous cost to patients and insurance companies, the FDA would not approve it for IPF without a proper clinical trial. The IPF study was completed a few years ago, and it showed no effect of the drug on lung function. Again, people were hurt. One more illustration; this time for the power of positive trial results. My nephew, Jason, was diagnosed with advanced Hodgkin's lymphoma at age eleven. He graduated from the University of Michigan last year. He is alive today, thanks to the courage and intelligence of families before him who made the difficult decision to enroll their children in properly designed clinical trials.
No matter how encouraging it sounds, no result from the first trial can prove that sirolimus is effective for LAM. The outcome measures that we are using are effort-dependent tests that can be affected by state of mind and motivation. The only way to be sure that we are not fooling ourselves is to eliminate as many biases as possible; especially by blinding patient and physician to treatment status. I so admire the bravery and faith of LAM patients who have pledged their support to do this together and to do it right. LAM is the model for effective patient advocacy. Patients have moved the disease from obscurity to a targeted molecular therapy in under five years. The LAM community has set the standard for conducting clinical trials!
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