Treatment of Metabolic Alkalosis With Acetazolamide. Effect on the Length of Mechanical Ventilation.

Study Overview
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Brief Summary
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The purpose of this study is to analyze whether the treatment of metabolic alkalosis with acetazolamide in intubated patients with chronic obstructive pulmonary disease (COPD) or with obesity hypoventilation syndrome (OHS) reduces the length of mechanical ventilation (MV).

Detailed Description
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Metabolic alkalosis (MA) may reduce central respiratory drive, cardiac output and worsen oxygenation, leading to a delay in weaning from MV. Acetazolamide is a carbonic anhydrase inhibitor that is able to correct MA and to stimulate respiratory drive. There is a paucity of studies on the outcome of patients with MA under MV treated with acetazolamide. The primary objective of our study is to analyze whether the treatment of MA with acetazolamide in intubated patients with COPD or with OHS reduces the length of MV, reduces the length of ICU stay or ICU mortality. Complications associated with acetazolamide treatment will be also analyzed. Phase III double-blinded trial, with COPD or OHS patients under MV who have pH > 7,35 and bicarbonate > 28 mEq/L. Patients will be randomized to receive 500 mg of acetazolamide or placebo. According to arterial blood gas analysis (ABGA) values treatment administration will be evaluated daily until extubation.

Official Title
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Effects of Acetazolamide on the Duration of Mechanical Ventilation in Patients With Metabolic Alkalosis. Phase III Multicenter Double-blinded Clinical Trial.

Conditions
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Pulmonary Disease, Chronic Obstructive, Obesity Hypoventilation Syndrome, Metabolic Alkalosis

Intervention / Treatment
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* Drug: Acetazolamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with COPD or obesity hypoventilation syndrome on invasive mechanical ventilation during less than 72 h with metabolic alkalosis, defined as a pH > 7.35 and actual bicarbonate > 28 mmol/L, and with potassium plasmatic levels >= 4 mEq/L. Exclusion Criteria: Postoperative patients. Previous psychiatric disease. Epilepsy. Pregnancy. Hepatic cirrhosis. Sulfonamide or acetazolamide allergy. Plasmatic creatinine > 2.5 mg/dL or creatinine clearance < 20 mL/min or continuous renal replacement techniques. Intolerance to enteral feeding. Administration in the previous 72 h of bicarbonate or acetazolamide. Terminal disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetazolamide<br> | Drug: Acetazolamide<br>* Daily morning ABGA: If actual bicarbonate > 26 mmol/L and pH > 7.35: administration of enteral capsule of acetazolamide 500 mg . If actual bicarbonate > 26 mmol/L and pH <= 7.35, increase minute ventilation to reach pH > 7.35 and then administer enteral capsule of acetazolamide 500 mg. If actual bicarbonate <= 26 mmol/L: omit treatment that day.<br>* Other names: Edemox;|
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* Daily morning ABGA: If actual bicarbonate > 26 mmol/L and pH > 7.35: administration of enteral capsule of placebo. If actual bicarbonate > 26 mmol/L and pH <= 7.35, increase minute ventilation to reach pH > 7.35 and then administer enteral capsule of placebo. If actual bicarbonate <= 26 mmol/L: omit treatment that day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of mechanical ventilation |  | From intubation date to extubation date, an expected average of 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of intensive care unit stay |  | The duration of ICU stay, an expected average less than 2 weeks | 
| All cause hospital mortality | Alive or dead status will be recorded at the end of hospital stay | Participants will be followed for the duration of hospital stay, an expected average of 3 weeks | 
| Complications associated to the treatment | Plasma and urine analysis will be performed to detect alteration in electrolites or renal function. | During the mechanical ventilation period, an expected average of 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Disease, Chronic Obstructive, Obesity Hypoventilation Syndrome, Alkalosis, Respiration, Artificial, Acetazolamide, Intensive care, Adult