Aztreonam Aerosol to Treat Cystic Fibrosis Nasal Disease

NCT ID: NCT02730793

Last Updated: 2021-01-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-09-19

Brief Summary

This study is designed as a masked, two center, randomized, placebo-controlled pilot study to evaluate the safety and efficacy of nasal and oral inhalation of 75 mg aztreonam in subjects with CF and lung infection due to PA. The study will involve two sites: Virginia Commonwealth University Medical Center (VCU) and Eastern Virginia Medical School (EVMS). Potential subjects will be identified in each site's CF clinic.

Detailed Description

This study is designed to explore the efficacy and safety of nasal aztreonam administered using the Pari Sinus Nebulizer combined with oral Cayston aerosol therapy compared to placebo on clinical and laboratory endpoints such as risk of antibiotic-resistant Pseudomonas aeruginosa (PA), time to pulmonary infection exacerbation, nasal quality of life, pulmonary function, nasal and lower airway cultures, and properties of mucus.

P. aeruginosa (PA) is a primary cause of lung infections in persons with cystic fibrosis (CF) (1). Over the past decade, studies have shown that aerosolized antibiotics can reduce lower respiratory bacterial load, decrease exacerbations of pulmonary disease, and in many patients improve pulmonary function. Cayston (aztreonam) oral aerosol using the PARI Altera Nebulizer System was approved by the FDA in February 2010 for CF patients 7 years of age or older with PA (2). In 2011, 35.8% or patients in the National CF Patient Registry used Cayston for treatment (3). Bacterial cultures suggest that the upper airways and lower airways of CF patients are cross-infected by PA and that the paranasal sinuses can act as a bacterial reservoir (4). There is improved post-transplanation patient survival for recipients that undergo sinus surgery and daily nasal washes to reduce bacterial load (2).

Routine CF care does not generally include upper airway assessment. There are no published studies evaluating the effect of aerosol antibiotics to treat nasal and sinus infections in CF in combination with oral inhaled aerosol therapy to treat the lower airway disease. However Mainz and colleagues published a case report that suggested that sinonasal administration of tobramycin using the Pari Sinus nebulizer (Pari Corp, Starnberg, Germany) delayed PA lower respiratory infection in a 12 year-old with CF who had chronic mucopurulent rhinosinusitis (5) and studies in chronic obstructive pulmonary disease suggest that treating upper airways can also improve coexistent lower airway disease.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Standard Therapy

Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Nasal Placebo-Normal Saline twice per day

Group Type: ACTIVE_COMPARATOR

Oral Aztreonam

Intervention Type: DRUG

Standard Therapy Comparator (Oral Cayston 75mg three times a day)

Nasal Placebo

Intervention Type: DRUG

Placebo (nasal saline twice per day)

Study Therapy

Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Experimental- Nasal Aztreonam 75 mg twice per day

Group Type: EXPERIMENTAL

Oral Aztreonam

Intervention Type: DRUG

Standard Therapy Comparator (Oral Cayston 75mg three times a day)

Nasal Aztreonam

Intervention Type: DRUG

Study Therapy (nasal Aztreonam 75mg twice per day)

Interventions

Oral Aztreonam

Standard Therapy Comparator (Oral Cayston 75mg three times a day)

Intervention Type: DRUG

Nasal Aztreonam

Study Therapy (nasal Aztreonam 75mg twice per day)

Intervention Type: DRUG

Nasal Placebo

Placebo (nasal saline twice per day)

Intervention Type: DRUG

Other Intervention Names

Cayston; Azactam; Cayston; Azactam; Saline

Eligibility Criteria

Inclusion Criteria

1. Males or females 7 years of age or older and able to perform pulmonary function testing

2. Confirmed diagnosis of CF by the 1997 CF Consensus Conference criteria and followed by the VCU or EVMS CF clinic

3. Presence of PA in 2 lower respiratory tract (sputum) cultures in the 24 months before screening

4. Subjects and/or parent guardian must be able to give written informed consent prior to any study related procedure

5. All sexually active female subjects who are of childbearing potential must agree to use an effective method of contraception (i.e.condoms or abstinence).

6. All sexually active female subjects must have a negative pregnancy test at screening (V0).

7. Clinically stable determined by the study physician with no significant new respiratory symptoms.

8. Presence of PA in nasal culture (swab or secretion) or sinus culture obtained in the 12 months before screening or at screening visit

Exclusion Criteria

1. Use of oral, IV or inhaled antibiotics within 0 days before study other than low dose azithromycin

2. Severe pulmonary disease with FEV1<30% predicted of baseline SpO2<0.90

3. ENT surgery within 6 months of screening

4. Allergy or documented adverse reaction to aztreonam

5. Epistaxis or significant (>30mL) hemoptysis in the past 6 months

6. Frequent (weekly or more frequently) or severe headaches

7. Subject is unlikely to comply with the procedures scheduled in the protocol

8. Subject participates in another clinical trial within 30 days prior to study entry

9. Subjects who have had a lung transplant will be excluded

10. Prisoners will be excluded

11. Non-English Speaking patients will be excluded

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eastern Virginia Medical School

OTHER

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruce K Rubin, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Children's Hospital of Richmond at VCU

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HM20005657

Identifier Type: -

Identifier Source: org_study_id