Clinical trial NCT01499485: Treatment of Metabolic Alkalosis With Acetazolamide. Effect on the Length of Mechanical Ventilation.
Official title: Effects of Acetazolamide on the Duration of Mechanical Ventilation in Patients With Metabolic Alkalosis. Phase III Multicenter Double-blinded Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Obesity Hypoventilation Syndrome
Metabolic Alkalosis
Keywords: Pulmonary Disease, Chronic Obstructive
Obesity Hypoventilation Syndrome
Alkalosis
Respiration, Artificial
Acetazolamide
Intensive care
Adult
Lead sponsor: Hospital Son Llatzer
Sponsor class: OTHER
First posted: 2011-12-26
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Length of mechanical ventilation
timeFrame: From intubation date to extubation date, an expected average of 1 week
Secondary outcomes:
measure: Length of intensive care unit stay
timeFrame: The duration of ICU stay, an expected average less than 2 weeks
measure: All cause hospital mortality
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 3 weeks
measure: Complications associated to the treatment
timeFrame: During the mechanical ventilation period, an expected average of 1 week
Other outcomes:
Locations:
city: Granollers
country: Spain
facility: Fundació Hospital Asil de Granollers
state: Barcelona
city: Sant Joan Despí
country: Spain
facility: Hospital de Sant Joan Despí Moisès Broggi
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
state: Comunidad de Madrid
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
state: Comunidad de Madrid
city: Manacor
country: Spain
facility: Hospital de Manacor
state: Illes Balears
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
state: Illes Balears
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtzer
state: Illes Balears
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
Study officials:
References:
citation: Faisy C, Mokline A, Sanchez O, Tadie JM, Fagon JY. Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation. Intensive Care Med. 2010 May;36(5):859-63. doi: 10.1007/s00134-010-1795-7. Epub 2010 Mar 9.
citation: Raurich JM, Rialp G, Ibanez J, Llompart-Pou JA, Ayestaran I. Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO(2) response and acetazolamide treatment effects. Respir Care. 2010 Nov;55(11):1442-8.
citation: Mazur JE, Devlin JW, Peters MJ, Jankowski MA, Iannuzzi MC, Zarowitz BJ. Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: a randomized, double-blind trial. Crit Care Med. 1999 Jul;27(7):1257-61. doi: 10.1097/00003246-199907000-00004.
citation: Banga A, Khilnani GC. Post-hypercapnic alkalosis is associated with ventilator dependence and increased ICU stay. COPD. 2009 Dec;6(6):437-40. doi: 10.3109/15412550903341448.
citation: Moviat M, Pickkers P, van der Voort PH, van der Hoeven JG. Acetazolamide-mediated decrease in strong ion difference accounts for the correction of metabolic alkalosis in critically ill patients. Crit Care. 2006 Feb;10(1):R14. doi: 10.1186/cc3970.
citation: Rialp Cervera G, Raurich Puigdevall JM, Moran Chorro I, Martin Delgado MC, Heras la Calle G, Mas Serra A, Vallverdu Perapoch I. Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease or obesity-hypoventilation syndrome with metabolic alkalosis. A randomized trial. Pulm Pharmacol Ther. 2017 Jun;44:30-37. doi: 10.1016/j.pupt.2017.03.002. Epub 2017 Mar 7.