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Protocol Details

A Randomized, Double-Blind, Placebo Controlled Study of Liposomal Amikacin for Inhalation (Arikace ) in Patients with Recalcitrant Nontuberculous Mycobacterial Lung Disease

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

12-I-0133

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 75

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Cystic Fibrosis;
Bronchlectasis;
Inhalation Antibiotic;
Non-Tuberculous Mycobacteria

Recruitment Keyword(s)

None

Condition(s)

Nontuberculous Mycobacteria;
Cystic Fibrosis;
Bronchiectasis

Investigational Drug(s)

ARIKACE

Investigational Device(s)

None

Intervention(s)

Drug: Inhalational Antibiotic

Supporting Site

National Institute of Allergy and Infectious Diseases

Background:

- Nontuberculous mycobacteria (NTM) are germs common to water and soil that do not usually affect healthy people. People with cystic fibrosis and other lung problems, however, have difficulty clearing mucus from their lungs. Because of this mucus buildup, these people are more likely to develop NTM lung infections. Chronic or long-term NTM infections may lead to more lung function problems. However, most of the drugs used to treat NTM infections are not well tolerated and not always effective.

- Arikace is an experimental drug that may help treat NTM infections. It is an antibiotic that has been modified to reduce severe side effects, such as hearing loss or kidney problems. Researchers want to test it with a nebulizer (medication inhaler) to get the medicine directly to the lungs. This helps target infected cells and spares normal cells, such as those in the ears and kidneys, from severe side effects.

Objectives:

- To test the safety and effectiveness of Arikace for NTM lung infections.

Eligibility:

- Individuals between 18 and 75 years of age who have chronic lung infection with either Mycobacterium avium complex or Mycobacterium abscessus that is unresponsive to standard therapy.

Design:

- Participants will be screened with a physical exam and medical history. Blood, urine, and sputum samples will be collected. Heart and lung function tests will be given. Participants may also have hearing tests and lung imaging studies.

- Participants will have either Arikace or a placebo for 12 weeks. At the end of 12 weeks, all participants will have the option to receive an additional 12 weeks of Arikace only (no placebo).

- The study drug will be inhaled with a nebulizer. It will take about 15 minutes to completely inhale the drug. Participants will use the nebulizer every day for the full 12 weeks.

- Participants will be monitored with study visits about every 4 weeks. The visits will involve many of the same tests given in the screening visit.

- Participants will have two final followup visits about 12 and 24 months after the last dose of the study drug.

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Eligibility

Subjects must have a primary care provider.

INCLUSION CRITERIA:

To be eligible to participate in this study, each subject must satisfy all of the following inclusion criteria:

1. Male or female patients, ages 18 years to 75 years.

2. Diagnosis of pulmonary nontuberculous mycobacterial lung disease in accordance with the 2007 ATS/IDSA criteria with evidence of nodular bronchiectasis and/or fibrocavitary disease by chest computed tomography (CT).

3. History of chronic infection defined as at least 2 documented positive cultures in the prior 2 years, of which at least one was obtained in the 6 months prior to screening with either Mycobacterium avium complex or Mycobacterium abscessus or mixed infection with both species (NTM contaminants M. gordonae, M. haemophilum, M. mucogenicum, M. nonchromogenicum, and M. terrae complex are allowed as long as MAC and/or M. abscessus are the predominant organism). The cultures could have been obtained from sputum or bronchoscopy.

4. Positive sputum culture obtained during the screening period with either Mycobacterium avium complex or Mycobacterium abscessus or mixed infection with one dominant species.

5. Receiving ATS/IDSA guidelines-based treatment regimen defined as: adherent to a multi-drug regimen for at least 6 months prior to screening with persistently positive mycobacterial cultures.

6. Ability to produce at least 3.0 mL of sputum or be willing to undergo an induction that produces at least 3.0 mL of sputum for mycobacteriology.

7. Female of childbearing potential agrees to practice an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD).

8. Written informed consent or assent obtained from the patient, parent or legal guardian prior to the performance of any study related procedures.

9. Willingness to have specimens stored.

10. Ability to comply with study medication use, study visits, and study procedures as determined by the investigator.

EXCLUSION CRITERIA:

A subject will be ineligible to participate in this study if any of the following criteria are satisfied or true:

1. Forced Expiratory Volume in 1 second (FEV1) < 30% of predicted at screening.

2. Presence of any clinically significant cardiac disease as determined by Investigator: The QTc criteria for exclusion of subjects is:

males QTc> 450 msec (or 0.450 seconds)

females QTc> 470 msec (or 0.470 seconds)

3. Subjects with hemoptysis of greater than or equal to 60 mL in a 24 hour period within 4 weeks prior to screening.

4. Positive pregnancy test or lactation at screening. All women of child bearing potential will be tested. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.

5. Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within one year prior to screening or anticipated during the study period.

6. Active allergic bronchopulmonary mycosis or any other condition requiring systemic steroids at a dose > equivalent of 10 mg/day of prednisone within 3 months prior to screening.

7. Pulmonary tuberculosis requiring treatment or treated within 2 years prior to screening.

8. History of lung transplantation.

9. History of acute pulmonary exacerbation requiring treatment with antibiotics within 4 weeks prior to screening or anytime during screening.

10. History of acute upper respiratory infection within 2 weeks prior to screening or anytime during screening

11. Radiographic finding of new lobar consolidation, atelectasis, significant pleural effusion, or pneumothorax within 2 months prior to or at the time of screening.

12. Initiation of chronic therapy (e.g., high-dose ibuprofen, inhaled anti-inflammatory agents including steroids, low dose maintenance steroids, rhDNase, chronic suppressive antibacterial treatment) within the 28 days prior to screening.

13. Administration of any investigational drug within 8 weeks prior to screening.

14. Prior exposure to Arikace (including clinical study).

15. Hypersensitivity to aminoglycosides.

16. Use of inhaled antibiotics, systemic aminoglycosides (e.g., tobramycin, amikacin, gentamicin or streptomycin) from the screening visit through Study Day 1 (including at least 28 days prior to Study Day 1).

17. Any change in chronic NTM multi-drug regimen within 28 days prior to Study Day 1.

18. Acquired and primary immunodeficiency syndromes.

19. Significant (as determined by the investigator) hearing loss, vestibular dysfunction, or neuromuscular weakness where the potential risk of aminoglycoside toxicity outweighs the potential benefit.

20. Evidence of biliary cirrhosis with portal hypertension.

21. Aspartate aminotransferase or alanine aminotransferase greater than or equal to 3 times the upper limit of normal at Screening.

22. Absolute Neutrophil Count less than or equal to 1000/(micro) L performed at screening.

23. Serum creatinine > 1.8 times normal performed at screening.

24. History of daily, continuous oxygen supplementation.

25. Smoking tobacco or any substance within 6 months prior to screening or anticipated inability to refrain from smoking throughout the study.

26. History of alcohol, medication or illicit drug abuse within the 1 year prior to screening.

27. Any condition which in the opinion of the Investigator interferes with ability to safely complete the study or adhere to study requirements.


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Citations:

Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, Holland SM, Horsburgh R, Huitt G, Iademarco MF, Iseman M, Olivier K, Ruoss S, von Reyn CF, Wallace RJ Jr, Winthrop K; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416.

Olivier KN, Weber DJ, Wallace RJ Jr, Faiz AR, Lee JH, Zhang Y, Brown-Elliot BA, Handler A, Wilson RW, Schechter MS, Edwards LJ, Chakraborti S, Knowles MR; Nontuberculous Mycobacteria in Cystic Fibrosis Study Group. Nontuberculous mycobacteria. I: multicenter prevalence study in cystic fibrosis. Am J Respir Crit Care Med. 2003 Mar 15;167(6):828-34.

Marras TK, Chedore P, Ying AM, Jamieson F. Isolation prevalence of pulmonary non-tuberculous mycobacteria in Ontario, 1997 2003. Thorax. 2007 Aug;62(8):661-6.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Kenneth N. Olivier, M.D.
National Heart, Lung and Blood Institute (NHLBI)
BG 10 RM 12C110
10 CENTER DR
BETHESDA MD 20814
(301) 496-5673
kenneth.olivier@nih.gov

Kenneth N. Olivier, M.D.
National Heart, Lung and Blood Institute (NHLBI)
BG 10 RM 12C110
10 CENTER DR
BETHESDA MD 20814
(301) 496-5673
kenneth.olivier@nih.gov

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

prpl@mail.cc.nih.gov

Clinical Trials Number:

NCT01315236

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