Condition category
Respiratory
Date applied
20/06/2011
Date assigned
29/06/2011
Last edited
25/02/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Mechanical ventilation is a method where a machine called a ventilator is used to assist or replace spontaneous breathing. Patients undergoing mechanical ventilation are frequently given prolonged and/or high doses of opioid drugs. When this stops, this can cause a withdrawal syndrome and difficulty in weaning from mechanical ventilation (reducing breathing support until the patient can breathe spontaneously). The aim of this study is to test whether giving patients methadone when weaning them from sedation and analgesia (painkillers) decreases the time it takes to wean them from mechanical ventilation.

Who can participate?
Critically ill adult patients undergoing mechanical ventilation and being treated with the painkiller fentanyl intravenously (delivered into a vein).

What does the study involve?
Participants are randomly allocated to one of two groups. For one group intravenous fentanyl is replaced with enteral methadone (enteral means that the drug is given by a tube placed in the nose, stomach or intestine). The other group undergo a gradual reduction of intravenous fentanyl. The duration of ventilation weaning, duration of mechanical ventilation, length of intensive care unit (ICU) stay and length of hospital stay are assessed in both groups.

What are the possible benefits and risks of participating?
The risks to participants are related to the side effects of methadone.

Where is the study run from?
Adult Intensive Care Units of four general hospitals in southern Brazil in the City of Joinville: Hospital Municipal São José, Centro Hospitalar Unimed, Hospital Dona Helena and Hospital Regional Hans Dieter Schmidt.

When is the study starting and how long is it expected to run for?
April 2005 to October 2009

Who is funding the study?
Sao Jose Municipal Hospital (Brazil)

Who is the main contact?
Dr Raquel Wanzuita
raquelwan@uol.com.br

Trial website

Contact information

Type

Scientific

Primary contact

Dr Raquel Wanzuita

ORCID ID

Contact details

Rua Orestes Guimarães
905
Joinville
89204-060
Brazil
+55 (0)47 3441 9798
raquelwan@uol.com.br

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial

Acronym

Study hypothesis

The introduction of enteral methadone during weaning from sedation and analgesia in critically ill adult patients on MV would decrease the weaning time from mechanical ventilation (MV)

Ethics approval

1. Ethics in Research of Hospital Municipal São José of Joinville, 15/10/2004, ref: 008
2. Ethics Committee for Review of Research Projects of Hospital of the Medical College of Medicine, University of Sao Paulo, 29/03/2006, ref: 0195/07

Study design

Prospective multicentre controlled randomized double-blind clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Mechanical ventilation in critically ill adult patients

Intervention

The enrolled patients were randomized into two groups: the methadone group (MG), for whom intravenous fentanyl was replaced with enteral methadone; and the control group (CG), who underwent a gradual reduction of intravenous fentanyl.
1. The MG received the following treatment:
1.1. One capsule of methadone (10 mg) was administered enterally every 6 hours
1.2. The rate of fentanyl infusion was reduced by 20%
1.3. After 24 hrs, the vial of fentanyl infusion was replaced by the study solution (placebo) and the infusion rate was reduced by 20%
1.4. The infusion rate for the placebo solution was reduced by 20% every 24 hours
2. The following schedule was applied for the CG:
2.1. A placebo capsule was administered enterally every 6 hrs
2.2. The rate of fentanyl infusion was reduced by 20%
2.3. After 24 hrs, the vial of fentanyl was replaced by the study solution (fentanyl) and the infusion rate was reduced by 20%
2.4. The infusion rate for the fentanyl solution was reduced by 20% every 24 hrs
3. Occasional episodes of intolerance to opioid withdrawal, characterized by agitation, anxiety, tremors, myoclonus, vomiting, diarrhea, piloerection, sweating, dilated pupils, tachycardia and hypertension, were treated with supplemental opioids as follows:
3.1. Bolus 1-2 g/kg of fentanyl
3.2. Increase the capsule dose (methadone/placebo) by 50%
3.3. Increase the infusion rate of the solution (fentanyl/placebo) to the previous dose

The study solutions and capsules were handled, identified and released by a pharmacist, who was the only person that knew the nature of the administered drugs. The capsules contained starch or 10 mg of methadone and were indistinguishable in appearance. The solutions contained 100ml of saline or 50ml of saline and 50ml of fentanyl, also indistinguishable by sight.

The main variables assessed were the following: duration of ventilation weaning (weaning success was defined as 48 hours without reinstitution of mechanical ventilation), duration of mechanical ventilation, length of intensive care unitc (ICU) stay and length of hospital stay. The clinical and demographic data collected included age, sex, weight, indications for hospitalization, comorbidities (hypertension, diabetes mellitus, chronic lung disease, psychiatric and neurological disorders, obesity, alcoholism, smoking or illicit drug use), the information necessary to calculate the Acute Physiology And Chronic Health Evaluation (APACHE) II and deaths before and after discharge from the ICU. Also recorded were the following factors: need for supplemental doses of fentanyl for the treatment of opioid withdrawal intolerance, accumulated doses of fentanyl and midazolam maleate used before the start of weaning and the use of other sedatives.

Intervention type

Drug

Phase

Not Applicable

Drug names

Methadone, fentanyl

Primary outcome measures

Duration of ventilation weaning (weaning success was defined as 48 hrs without reinstitution of mechanical ventilation)

Secondary outcome measures

1. Duration of mechanical ventilation
2. Length of ICU stay
3. Length of hospital stay

Overall trial start date

29/04/2005

Overall trial end date

19/10/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. The subjects studied were severely ill patients who required MV and the continuous use of fentanyl and who met the following inclusion criteria:
1.1. MV for at least five days
1.2. The use of fentanyl analgesia in varying doses for at least five day or
1.3. A dose of fentanyl more than or equal to 5 µg/kg/h for at least 12 days.
2. Subjects were also required to meet the following ventilation weaning criteria:
2.1. Reversal of the process that caused the respiratory failure
2.2. Adequate oxygenation (PaO2/FiO2) > 200
2.3. Positive end-expiratory pressure (PEEP) less than or equal to 5; FiO2 less than or equal to 0.4 and pH more than or equal to 7.25
2.4. Hemodynamic stability (with minimal or no vasoactive drugs) and neurological stability (ability to initiate respiratory effort)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

75 patients were randomized

Participant exclusion criteria

1. Patients younger than 18 years
2. Patients with terminal diseases
2. Patients with cervical spinal cord injuries or neuromuscular diseases

Recruitment start date

29/04/2005

Recruitment end date

19/10/2009

Locations

Countries of recruitment

Brazil

Trial participating centre

Rua Orestes Guimarães, 905
Joinville
89204-060
Brazil

Sponsor information

Organisation

Sao Jose Municipal Hospital (Brazil)

Sponsor details

Avenida Getulio Vargas
238
Joinville
89202-000
Brazil
+55 (0)47 3441 6666
clinicamedica_hmsj@yahoo.com.br

Sponsor type

Hospital/treatment centre

Website

http://www.hmsj.sc.gov.br

Funders

Funder type

Hospital/treatment centre

Funder name

Sao Jose Municipal Hospital (Brazil)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

25/02/2016: Plain English summary added.