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

Sponsor

Hospital Son Llatzer (Other)

Overall Status

Completed

CT.gov ID

NCT01499485

Collaborator

(none)

140

Enrollment

Locations

Arms

Duration (Months)

17.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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).

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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.

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Feb 1, 2015

Actual Study Completion Date :

Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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.

Arm

Intervention/Treatment

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 Names:

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.

Outcome Measures

Primary Outcome Measures

Length of mechanical ventilation [From intubation date to extubation date, an expected average of 1 week]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Fundació Hospital Asil de Granollers	Granollers	Barcelona	Spain	08402
2	Hospital de Sant Joan Despí Moisès Broggi	Sant Joan Despí	Barcelona	Spain	08970
3	Hospital Universitario Infanta Leonor	Madrid	Comunidad de Madrid	Spain	28031
4	Fundación Jiménez Díaz	Madrid	Comunidad de Madrid	Spain	28040
5	Hospital de Manacor	Manacor	Illes Balears	Spain	07500
6	Hospital Son Espases	Palma de Mallorca	Illes Balears	Spain	07010
7	Hospital Son Llàtzer	Palma de Mallorca	Illes Balears	Spain	07198
8	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08025