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

NCT ID: NCT01499485

Last Updated: 2015-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-02-28

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Acetazolamide

Group Type: EXPERIMENTAL

Acetazolamide

Intervention Type: DRUG

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.

placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Acetazolamide

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Edemox

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Son Llatzer

OTHER

Sponsor Role: lead

Responsible Party

Gemma Rialp

MD; PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hospital de Manacor

Manacor, Balearic Islands, Spain

Hospital Son Espases

Palma de Mallorca, Balearic Islands, Spain

Hospital Son Llàtzer

Palma de Mallorca, Balearic Islands, Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Fundació Hospital Asil de Granollers

Granollers, Barcelona, Spain

Hospital de Sant Joan Despí Moisès Broggi

Sant Joan Despí, Barcelona, Spain

Hospital Universitario Infanta Leonor

Madrid, Madrid, Spain

Fundación Jiménez Díaz

Madrid, Madrid, Spain

Countries

Spain

References

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.

Reference Type: BACKGROUND

PMID: 20217045 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20979670 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10446816 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19938966 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16420662 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28286047 (View on PubMed)

Other Identifiers

TRAMA study

Identifier Type: -

Identifier Source: org_study_id