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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gemma Rialp, Hospital Son Llatzer
ClinicalTrials.gov Identifier:
NCT01499485
First received: December 20, 2011
Last updated: March 16, 2015
Last verified: March 2015
  Purpose
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).

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Obesity Hypoventilation Syndrome
Metabolic Alkalosis
Drug: Acetazolamide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Acetazolamide on the Duration of Mechanical Ventilation in Patients With Metabolic Alkalosis. Phase III Multicenter Double-blinded Clinical Trial.

Resource links provided by NLM:


Further study details as provided by Hospital Son Llatzer:

Primary Outcome Measures:
  • Length of mechanical ventilation [ Time Frame: From intubation date to extubation date, an expected average of 1 week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Length of intensive care unit stay [ Time Frame: The duration of ICU stay, an expected average less than 2 weeks ] [ Designated as safety issue: No ]
  • All cause hospital mortality [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3 weeks ] [ Designated as safety issue: No ]
    Alive or dead status will be recorded at the end of hospital stay

  • Complications associated to the treatment [ Time Frame: During the mechanical ventilation period, an expected average of 1 week ] [ Designated as safety issue: Yes ]
    Plasma and urine analysis will be performed to detect alteration in electrolites or renal function.


Enrollment: 140
Study Start Date: November 2011
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acetazolamide 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.
Other Name: Edemox
Placebo Comparator: placebo 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.

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01499485

Locations
Spain
Fundació Hospital Asil de Granollers
Granollers, Barcelona, Spain, 08402
Hospital de Sant Joan Despí Moisès Broggi
Sant Joan Despí, Barcelona, Spain, 08970
Hospital Universitario Infanta Leonor
Madrid, Comunidad de Madrid, Spain, 28031
Fundación Jiménez Díaz
Madrid, Comunidad de Madrid, Spain, 28040
Hospital de Manacor
Manacor, Illes Balears, Spain, 07500
Hospital Son Espases
Palma de Mallorca, Illes Balears, Spain, 07010
Hospital Son Llàtzer
Palma de Mallorca, Illes Balears, Spain, 07198
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Sponsors and Collaborators
Hospital Son Llatzer
  More Information

Publications:
Responsible Party: Gemma Rialp, MD; PhD, Hospital Son Llatzer
ClinicalTrials.gov Identifier: NCT01499485     History of Changes
Other Study ID Numbers: TRAMA study 
Study First Received: December 20, 2011
Last Updated: March 16, 2015
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Hospital Son Llatzer:
Pulmonary Disease, Chronic Obstructive
Obesity Hypoventilation Syndrome
Alkalosis
Respiration, Artificial
Acetazolamide
Intensive care
Adult

Additional relevant MeSH terms:
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Hypoventilation
Obesity Hypoventilation Syndrome
Alkalosis
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive
Respiratory Insufficiency
Respiration Disorders
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Apnea, Obstructive
Sleep Apnea Syndromes
Apnea
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Obesity
Overnutrition
Nutrition Disorders
Acid-Base Imbalance
Metabolic Diseases
Acetazolamide
Anticonvulsants
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 25, 2016