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

Pulmonary Disease, Chronic Obstructive Clinical Trial

— TRAMA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01499485
• Other study ID #: TRAMA study
• Status: Completed
• Phase: Phase 3
• First received: December 20, 2011
• Last updated: March 16, 2015
• Start date: November 2011
• Est. completion date: February 2015

Study information

• Verified date: March 2015
• Source: Hospital Son Llatzer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alkalosis
• Chronic Disease
• Hypoventilation
• Lung Diseases
• Metabolic Alkalosis
• Obesity Hypoventilation Syndrome
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Fundació Hospital Asil de Granollers	Granollers	Barcelona
Spain	Fundación Jiménez Díaz	Madrid	Comunidad de Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid	Comunidad de Madrid
Spain	Hospital de Manacor	Manacor	Illes Balears
Spain	Hospital Son Espases	Palma de Mallorca	Illes Balears
Spain	Hospital Son Llàtzer	Palma de Mallorca	Illes Balears
Spain	Hospital de Sant Joan Despí Moisès Broggi	Sant Joan Despí	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Son Llatzer

Country where clinical trial is conducted

Spain, 

References & Publications (5)

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. — View Citation

Faisy C, Mokline A, Sanchez O, Tadié 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. — View 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. — View 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. — View Citation

Raurich JM, Rialp G, Ibáñez J, Llompart-Pou JA, Ayestarán I. Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO2 response and acetazolamide treatment effects. Respir Care. 2010 Nov;55(11):1442-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of mechanical ventilation		From intubation date to extubation date, an expected average of 1 week	No
Secondary	Length of intensive care unit stay		The duration of ICU stay, an expected average less than 2 weeks	No
Secondary	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	No
Secondary	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	Yes