Optimising inhaled mannitolfor cystic fibrosis in an adult

population AF Patrick, LA Moira, B Diana..et al

Done By :Al Yaqdhan Al Atbi, MD

Outline

• Introduction• Mannitol/ Mannitol inhaler• Literature Review• Study: Aim, methodology, results,

discussion, conclusion.

Introduction

Introduction

• CF chronic airway infection and inflammation.

• Airway clearance therapies (ACTs) is a primary therapy for CF patients.– Inhaled hypertonic saline – Recombinant human DNAase

Mannitol• Naturally occurring sugar alcohol• Dry powder formulated.

• Mechanism of Action:– Change the viscoelastic properties of airway phlegm– Increase the hydration of the airway surface liquid

increased clearance of the retained secretions through mucociliary activity and productive cough.

Mannitol Inhaler

Literature Review

• phase 3 studies (CF301 and CF302):

– Investigate the safety and efficacy of inhaled mannitol in subjects with CF over a period of 6 months.

– These studies demonstrated clinically relevant benefits of inhaled mannitol.

– Inhaled mannitol was recently approved for use in adults in Europe.

Aims:

– To discuss the importance of airway clearance treatments in the management of cystic fibrosis.

– To describe the clinical data that supports the use of mannitol in adult patients with cystic fibrosis.

– To highlight the role of mannitol tolerance testing in screening for hyperresponsiveness.

– To provide practical considerations for patient education in use of mannitol inhaler

Methodology

• Multicentre, randomised, controlled, parallel-arm, double-blind

• phase III clinical trial to determine the efficacy and safety of inhaled dry powder

• Pooled Data from CF301, CF302.– Adults > 18 years– Sample size: 390– Subjects:

• diagnosed patient with CF • FEV1 range 30-90% (CF301); 40-90% (CF302)

Cont.. Methodology

• Continuation of all approved CF therapies.

• Mannitol Tolerance Test (MTT):

• subjects were randomised 3:2

• 2phases:– Phase I: 26 weeks (control 50 mg BID, study group 400mg

BID)– Phase II: 26 weeks optional , open-Labeled , all subjects

received 400mg BID mannitol.

Results

Results

Cont.. Results

Cont.. Results

Cont.. Results

• Withdrawals, education and compliance:– CF301: withdrawal rate 35.3 %– CF302: withdrawal rate 20.5%

• Mannitol was well tolerated by adult subjects with CF, although there was a higher drop-out rate overall in the mannitol group compared with the control group

42% reduction in withdrawal rate

Cont.. Results

• Factors that may influence adherence to mannitol inhaler:

• Simple• Portable• disposable.• requires no special care • not require sterilisation

Positive factors:

•Excessive coughing on inhalation•No perceived short-term benefit

Negative factors:

Discussion:• Inhaled mannitol is a safe, effective treatment for adult patients

with CF, and it can be used in addition to best standard care.

• The differences in the withdrawal rates between studies CF301 and CF302 – Indicates the importance of education and training.

• MTT is an effective screening procedure to identify those patients at risk for bronchospasm.

• MTT provides opportunity to educate patients about the proper use of the inhaler.

Tips for use of inhaled mannitol

• Only remove capsules immediately before use.• Pierce capsules once only.• Tilt inhaler so mouth-piece faces slightly downward• Breathe out completely away from the inhaler.• With the head tilted upwards, the patient should inhale deeply “rattling”

sound– The inhalation rate may be slowed down if coughing occurs

• After the dose from each capsule is inhaled, breath hold for 5 s • Exhale and cough AWAY from the inhaler to prevent humidity build-up

within the device.

• The 10 capsules should be taken closely together over a 3–5 min.• A sip of water may be taken throughout the challenge to relieve cough

and/or dry throat.

Conclusion

• Inhaled mannitol is now available for adult patients with CF as an adjunctive therapy to augment airway clearance.

• THANK YOU