Treatment of Metabolic Alkalosis in Acute Exacerbations of Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

Salt Replacement for Metabolic Alkalosis in Acute Exacerbations of Cystic Fibrosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00163852
• Other study ID #: 14/04
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: September 12, 2005
• Last updated: September 12, 2005
• Start date: February 2004
• Est. completion date: February 2006

Study information

• Verified date: September 2005
• Source: Bayside Health
• Contact: Alan C Young, MBBS, FRACP
• Phone: 613 9276 2000
• Email: alan.young[@]med.monash.edu.au
• Is FDA regulated: No
• Health authority: Australia: Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

Adult cystic fibrosis (CF) patients admitted with an acute infection complicated by acid-base disturbance and decreased ventilation will be studied.

They will receive salt replacement to correct the acid-base disturbance and possibly their ventilation.

Assessment of symptoms (questionnaire), acid-base and electrolyte status (blood and urine tests) ventilation (overnight oxygen and carbon dioxide monitoring non-invasively) and sleep-wake pattern (actigraphy) will be carried out.

Study hypothesis: Acute volume and electrolyte replacement corrects hypochloremic hypovolemic metabolic alkalosis and compensatory hypoventilation/ hypercapnia in acute exacerbations of cystic fibrosis.

Description:

Background: Hypochloremic hypovolemic metabolic alkalosis contributes to hypercapnia in acute exacerbations of cystic fibrosis. Treatment of the metabolic alkalosis with volume and sodium chloride (NaCl) replacement could reduce hypoventilation and hypercapnia, thereby improving symptoms, sleep patterns and daytime activity level. This would avoid unnecessary treatment with non-invasive ventilation.

Hypothesis: Volume and NaCl replacement corrects hypochloremic hypovolemic metabolic alkalosis and compensatory hypoventilation/ hypercapnia in acute exacerbations of cystic fibrosis and results in symptomatic improvement.

Entry criteria:

• Adult cystic fibrosis patient

• Admission with acute exacerbation

• PaCO2 > 45 mmHg

• Primary metabolic alkalosis (acid-base diagram of Stinebaugh and Austin)

• Serum chloride (Cl) ≤ 98 mmol/L

• Serum albumin (alb) > 25 mmol/L

Intervention:

• Normal saline intravenously day(D)1,2,3. (Replace greater of Cl deficiency or acute weight loss, with 2/3 on D1 and remainder D2, D3)

• NaCl tablets 3 tds D4 to 10 (calculated to replace 7 mmol NaCl loss in 60 kg subject)

Random allocation to either:

1. Intervention + standard care (including standard dietary advice) D1-10

2. Standard care alone (including standard dietary advice) D1-10

Primary outcome measures: (D1, D4, D10)

• PaCO2 (performed at same time of day as admission ABG’s)

• Acid-base status (Stinebaugh and Austin, ABG’s)

• Serum chloride

• Overnight oximetry (% night SpO2<90%) and PtcCO2 (rise in CO2 overnight)

Secondary outcome measures: (D1, D4, D10)

• Serum albumin, sodium

• Body mass index (BMI)

• Spirometry (D1, D10)

• Headache scale

• Epworth sleepiness scale

• Wrist actigraphy (circadian rhythm and daytime activity level)(D1-10)

• Urinary chloride, potassium, sodium, pH, osmolality

• Baseline ABG’s as stable outpatient (within 3 months, pre or post admission)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: February 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Adult cystic fibrosis patient

• Admission with acute exacerbation (criteria- fall in FEV1 > 10% from best in last 12/12, change in sputum volume and colour, new pulmonary infiltrate)

• PaCO2 > 45 mmHg on admission

• Primary metabolic alkalosis (acid-base diagram of Stinebaugh and Austin)

• Serum chloride (Cl) = 98 mmol/L

• Serum albumin (alb) = 25 mmol/L

Exclusion Criteria:

Concurrent diuretic therapy Concurrent glucocorticoid therapy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alkalosis
• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Normal saline IV, salt tablets

Locations

Country	Name	City	State
Australia	The Alfred	Melbourne	Victoria

Sponsors (4)

Lead Sponsor	Collaborator
Bayside Health	Cystic Fibrosis Federation Australia, Monash University, National Health and Medical Research Council, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary outcome measures: (Day1, D4, D10)
Primary	•PaCO2 (performed at same time of day as admission ABG’s)
Primary	•Acid-base status (Stinebaugh and Austin, ABG’s)
Primary	•Serum chloride
Primary	•Overnight oximetry (% night SpO2<90%) and PtcCO2 (rise in CO2 overnight)
Secondary	Secondary outcome measures: (Day1, D4, D10)
Secondary	•Serum albumin, sodium
Secondary	•Body mass index (BMI)
Secondary	•Spirometry (D1, D10)
Secondary	•Headache scale
Secondary	•Epworth sleepiness scale
Secondary	•Wrist actigraphy (circadian rhythm and daytime activity level)(D1-10)
Secondary	•Urinary chloride, potassium, sodium, pH, osmolality
Secondary	•Baseline ABG’s as stable outpatient (within 3 months, pre or post admission)