Treatment of Metabolic Alkalosis in Acute Exacerbations of Cystic Fibrosis

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Normal saline IV, salt tablets	Phase 2; Phase 3

Detailed 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)

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Salt Replacement for Metabolic Alkalosis in Acute Exacerbations of Cystic Fibrosis
Study Start Date :	February 2004
Study Completion Date :	February 2006

Arms and Interventions

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Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Primary outcome measures: (Day1, D4, D10)
2. •PaCO2 (performed at same time of day as admission ABG’s)
3. •Acid-base status (Stinebaugh and Austin, ABG’s)
4. •Serum chloride
5. •Overnight oximetry (% night SpO2<90%) and PtcCO2 (rise in CO2 overnight)

Secondary Outcome Measures :

1. Secondary outcome measures: (Day1, D4, D10)
2. •Serum albumin, sodium
3. •Body mass index (BMI)
4. •Spirometry (D1, D10)
5. •Headache scale
6. •Epworth sleepiness scale
7. •Wrist actigraphy (circadian rhythm and daytime activity level)(D1-10)
8. •Urinary chloride, potassium, sodium, pH, osmolality
9. •Baseline ABG’s as stable outpatient (within 3 months, pre or post admission)

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Alan C Young, MBBS, FRACP	613 9276 2000 ext pager 4576	alan.young@med.monash.edu.au
Contact: Matthew T Naughton, MBBS, FRACP	613 9276 2000 ext 3770	m.naughton@alfred.org.au

Locations

Australia, Victoria
The Alfred	Recruiting
Melbourne, Victoria, Australia, 3181
Contact: Alan C Young, MBBS 613 9276 2000 ext pager 4576 alan.young@med.monash.edu.au
Sub-Investigator: Alan C Young, MBBS

Sponsors and Collaborators

Bayside Health

National Health and Medical Research Council, Australia

Monash University

Cystic Fibrosis Federation Australia

Investigators

Principal Investigator:	Matthew T Naughton, MBBS, MD	The Alfred

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

ClinicalTrials.gov Identifier:	NCT00163852 History of Changes
Other Study ID Numbers:	14/04
First Posted:	September 14, 2005
Last Update Posted:	September 14, 2005
Last Verified:	September 2005

Keywords provided by Bayside Health:

Cystic fibrosis; Metabolic alkalosis; Hypercapnia; Salt replacement

Additional relevant MeSH terms:

Fibrosis; Cystic Fibrosis; Alkalosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases	Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Acid-Base Imbalance; Metabolic Diseases