Pulmonary Disease, Chronic ObstructivePhase 3TRAMANCT01499485
Treatment of Metabolic Alkalosis With Acetazolamide. Effect on the Length of Mechanical Ventilation.
A Phase 3 study testing Acetazolamide in people with Pulmonary Disease, Chronic Obstructive and Obesity Hypoventilation Syndrome, run by Hospital Son Llatzer at 8 sites in Spain.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive, Obesity Hypoventilation Syndrome, Metabolic Alkalosis
- What is being tested?
- Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 8 sitesSpain
- Study dates
- Nov 2011to Feb 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Postoperative patients.
- Previous psychiatric disease.
- Epilepsy.
- Pregnancy.
- Hepatic cirrhosis.
- Sulfonamide or acetazolamide allergy.
Show all 10Show fewer
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Spain8 sites
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, 08025
Fundació Hospital Asil de Granollers
Granollers, Barcelona, 08402
Hospital Universitario Infanta Leonor
Madrid, Madrid, 28031
Fundación Jiménez Díaz
Madrid, Madrid, 28040
Hospital de Manacor
Manacor, Balearic Islands, 07500
Hospital Son Espases
Palma de Mallorca, Balearic Islands, 07010
Hospital Son Llàtzer
Palma de Mallorca, Balearic Islands, 07198
Hospital de Sant Joan Despí Moisès Broggi
Sant Joan Despí, Barcelona, 08970
About this study
Official title: Effects of Acetazolamide on the Duration of Mechanical Ventilation in Patients With Metabolic Alkalosis. Phase III Multicenter Double-blinded Clinical Trial.
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).
Read the 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
- Being tested
- Acetazolamide, Placebo
- Keywords
- Pulmonary Disease, Chronic Obstructive, Obesity Hypoventilation Syndrome, Alkalosis, Respiration, Artificial, Acetazolamide, Intensive care, Adult
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Obesity Hypoventilation Syndrome, Alkalosis, Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetazolamideDrug
Also called Edemox
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Acetazolamide | Experimental | Not described Receives: Drug: Acetazolamide |
| placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of mechanical ventilation
Measured: From intubation date to extubation date, an expected average of 1 week
Secondary outcomes (3)
Length of intensive care unit stay
Measured: The duration of ICU stay, an expected average less than 2 weeks
All cause hospital mortality
Alive or dead status will be recorded at the end of hospital stay
Measured: Participants will be followed for the duration of hospital stay, an expected average of 3 weeks
Complications associated to the treatment
Plasma and urine analysis will be performed to detect alteration in electrolites or renal function.
Measured: During the mechanical ventilation period, an expected average of 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2011 (estimated)
- Study startNov 2011
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Son Llatzer
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gemma Rialp, Hospital Son Llatzer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01499485
- Sponsor's protocol ID
- TRAMA study
- Acronym
- TRAMA
- Status last verified
- Mar 2015
- First submitted
- 20 Dec 2011
- Last updated
- 17 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 20217045Raurich 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.
PubMed 20979670Mazur 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.
PubMed 10446816Banga 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.
PubMed 19938966Moviat 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.
PubMed 16420662Rialp 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.
PubMed 28286047
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Acetazolamide on the Duration of Mechanical Ventilation in Patients With Metabolic Alkalosis. Phase III Multicenter Double-blinded Clinical Trial.
- ClinicalTrials.gov ID
- NCT01499485
- Acronym / sponsor ID
- TRAMA / TRAMA study
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Hospital Son LlatzerUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 26 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide | Experimental | Drug: Acetazolamide |
| placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (10 listed)
- Postoperative patients.
- Previous psychiatric disease.
- Epilepsy.
- Pregnancy.
- Hepatic cirrhosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetazolamideAlso: EdemoxDaily 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. | Drug | Acetazolamide |
| PlaceboDaily 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. | Drug | placebo |
Primary outcome
Length of mechanical ventilation
Time frame: From intubation date to extubation date, an expected average of 1 week
3 secondary outcomes
Length of intensive care unit stay
Time frame: The duration of ICU stay, an expected average less than 2 weeks
All cause hospital mortality
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 3 weeks
Complications associated to the treatment
Time frame: During the mechanical ventilation period, an expected average of 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2015.
- Background: PubMed 20217045Faisy 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.
- Background: PubMed 20979670Raurich 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.
- Background: PubMed 10446816Mazur 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.
- Background: PubMed 19938966Banga 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.
- Background: PubMed 16420662Moviat 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.
- Derived from this study: PubMed 28286047Rialp 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Acetazolamide in people with Pulmonary Disease, Chronic Obstructive and Obesity Hypoventilation Syndrome, run by Hospital Son Llatzer at 8 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Length of mechanical ventilation (time frame: From intubation date to extubation date, an expected average of 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01499485, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2015.