Mechanical VentilationPhase 4NCT03030911
Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients
A Phase 4 study testing Dexmedetomidine, Midazolam and Fentanyl in people with Mechanical Ventilation and Dexmedetomidine, run by Cairo University at 1 site in Egypt.
Trial summary
The aim of this study is to compare the effect of dexmedetomidine on resting energy expenditure in relation to the midazolam in critically ill patients using indirect calorimetry Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mechanical Ventilation, Dexmedetomidine, Midazolam
- What is being tested?
- Dexmedetomidine, Midazolam and Fentanyl
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jan 2017to 15 Mar 2018
- Phase
- Phase 4
- 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
- The study will be designed to recruit 30 critically-ill patients who will be admitted to the surgical ICU for ventilatory support and will be expected to continue for 2 days or longer.
Who cannot join
- Age < 18 years old.
- Pregnant patient.
- Serious central nervous system pathologies (traumatic brain injury, acute stroke, uncontrolled seizures).
- Patient who will require fraction of inspired oxygen more than 0.6.
- Air leak from the chest tube.
- Patient with body temperature > 39 Celsius.
Show all 14Show fewer
- Acute hepatitis or severe liver disease (Child-Pugh class C).
- Left ventricular ejection fraction less than 30%.
- Heart rate less than 50 beats/min.
- Second or third degree heart block.
- Systolic pressure < 90 mmHg despite of infusion of 2 vasopressors.
- Patients with known endocrine dysfunction.
- Patient with hypothermia
- Patient on Positive end expiratory pressure more than 14 cmH2o
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients: Randomized Controlled Study
The aim of this study is to compare the effect of dexmedetomidine on resting energy expenditure in relation to the midazolam in critically ill patients using indirect calorimetry
Read the detailed description
Caloric needs in critically-ill patients fluctuate significantly over the course of the disease which might expose patients to either malnutrition or overfeeding. Malnutrition is associated with deterioration of lean body mass, poor wound healing, increased risk of nosocomial infection, and weakened respiratory muscles. On the other hand overfeeding in medically compromised patients can promote lipogenesis, hyperglycemia, and exacerbation of respiratory failure. Many factors may affect the resting energy expenditure (REE) through manipulation of oxygen consumption (VO2).
Sedatives are important contributors to reduction of REE. The postulated mechanism of sedative-induced reduction of VO2 is inhibition of circulating catecholamine and pro-inflammatory cytokines.
Dexmedetomidine is a highly selective α2-adrenoceptor agonist. Stimulation of the α2-adrenoceptor in the central nervous system causes a 60-80% reduction in sympathetic outflow and endogenous catecholamine levels. It was found that perioperative use of α2 agonists decreased sympathetic activity with subsequent reduction of VO2 and REE. Moreover, dexmedetomidine, has some anti-inflammatory effect by inhibiting the pro-inflammatory cytokines which may cause additional reduction of REE in critically ill patient.
Midazolam is another important sedative that is frequently used in critically-ill patient. Terao et al. found that increasing the depth of sedation using midazolam, decreased oxygen consumption and REE. However, it remains unclear whether the effect of midazolam on REE is related to the drug itself or to the depth of sedation.
There is no direct comparison in the literature between dexmedetomidine and midazolam on REE.
- Conditions
- Mechanical Ventilation, Dexmedetomidine, Midazolam, Sedation
- Being tested
- Dexmedetomidine, Midazolam, Fentanyl, Indirect calorimetry
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex
The drug will be administered for sedation and its effect on basal metabolic rate will be investigated
MidazolamDrug
Also called dormicum
The drug will be administered for sedation and its effect on basal metabolic rate will be investigated
FentanylDrug
The drug will be administered in both groups
Indirect calorimetryDevice
Also called Calorimetry
The device will be used for measurement of basal metabolic rate
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine group | Active comparator | * Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug.
* Group I patients will have dexmedetomidine (0.075 µg.kg-1.mL-1). Dexmedetomidine infusion will be started at 0.15 µg.kg-1.hr-1 (2 mL.hr-1) and will be adjusted by 0.15 µg.kg-1.h-1 increments to a maximum of 0.75 µg/kg/h (10 ml.h-1)
* Intervention: indirect calorimetry Receives: Drug: Dexmedetomidine; Drug: Fentanyl; Device: Indirect calorimetry |
| midazolam group | Placebo comparator | * Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug.
* Group II patients will have midazolam (0.5 mg.mL-1). Midazolam will be started at 1 mg.h-1 (2 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (10 mL.h-1). All infusions will be adjusted by increments of 2 mL.hr-1 to maintain blinding. Patients in either group not adequately sedated by the maximum infusion rate of the study medication will receive a bolus dose of fentanyl 0.5 µg.kg-1.
* Intervention: indirect calorimetry Receives: Drug: Midazolam; Drug: Fentanyl; Device: Indirect calorimetry |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Resting energy expenditure after drug administration
Resting energy expenditure will be measured using indirect calorimetry via metabolic module on General Electric ventilator
Measured: The first baseline measurement will be taken before drug administration. The second measurement will be taken 24 hours after drug infusion.
Secondary outcomes (10)
Heart rate
number of heart beats per minute
Measured: 24 hours
arterial blood pressure
arterial blood pressure measured in mmHg
Measured: 24 hours
Richmond agitation and sedation scale
range from -5 (unarousable) to +4 (combative)
Measured: 24 hours
Plasma interleukin-1β level
determined by ELISA using a quantitative sandwich enzyme immunoassay technique
Measured: 24 hours
Tumor necrosis factor-α plasma concentration
Enzyme immunoassay
Measured: 24 hours
partial pressure of oxygen in arterial blood
the partial pressure of oxygen in arterial blood measured in mmHg
Measured: 24 hours
VO2
the oxygen consumption measured in mL/Kg/min
Measured: 24 hours
VCO2
carbon dioxide production measured in mL/Kg/min
Measured: 24 hours
end-tidal co2
the pressure of carbon dioxide in expired air measured in mmHg
Measured: 24 hours
cardiac output
the amount of blood pumped by the heart during one minute
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2017 (estimated)
- Study start1 Jan 2017
- Primary completion10 Mar 2018
- Study completion15 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mechanical VentilationStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmed Hasanin, Cairo University
- Investigators
- Mohamed Abdulatif, Professor, Study chair, Professor and member of research committee of anesthesia department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03030911
- Sponsor's protocol ID
- N-26-2016
- Status last verified
- Mar 2018
- First submitted
- 19 Jan 2017
- Last updated
- 27 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Walker RN, Heuberger RA. Predictive equations for energy needs for the critically ill. Respir Care. 2009 Apr;54(4):509-21.
PubMed 19327188Rubinson L, Diette GB, Song X, Brower RG, Krishnan JA. Low caloric intake is associated with nosocomial bloodstream infections in patients in the medical intensive care unit. Crit Care Med. 2004 Feb;32(2):350-7. doi: 10.1097/01.CCM.0000089641.06306.68.
PubMed 14758147Covelli HD, Black JW, Olsen MS, Beekman JF. Respiratory failure precipitated by high carbohydrate loads. Ann Intern Med. 1981 Nov;95(5):579-81. doi: 10.7326/0003-4819-95-5-579.
PubMed 6794409Fung EB. Estimating energy expenditure in critically ill adults and children. AACN Clin Issues. 2000 Nov;11(4):480-97. doi: 10.1097/00044067-200011000-00002.
PubMed 11288413
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients: Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT03030911
- Acronym / sponsor ID
- N-26-2016
- Conditions
- Mechanical Ventilation, Dexmedetomidine, Midazolam, Sedation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 10 Mar 2018 (actual)
- Study completion
- 15 Mar 2018 (actual)
- First posted
- 25 Jan 2017 (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 aim of this study is to compare the effect of dexmedetomidine on resting energy expenditure in relation to the midazolam in critically ill patients using indirect calorimetry
Detailed description
Caloric needs in critically-ill patients fluctuate significantly over the course of the disease which might expose patients to either malnutrition or overfeeding. Malnutrition is associated with deterioration of lean body mass, poor wound healing, increased risk of nosocomial infection, and weakened respiratory muscles. On the other hand overfeeding in medically compromised patients can promote lipogenesis, hyperglycemia, and exacerbation of respiratory failure. Many factors may affect the resting energy expenditure (REE) through manipulation of oxygen consumption (VO2).
Sedatives are important contributors to reduction of REE. The postulated mechanism of sedative-induced reduction of VO2 is inhibition of circulating catecholamine and pro-inflammatory cytokines.
Dexmedetomidine is a highly selective α2-adrenoceptor agonist. Stimulation of the α2-adrenoceptor in the central nervous system causes a 60-80% reduction in sympathetic outflow and endogenous catecholamine levels. It was found that perioperative use of α2 agonists decreased sympathetic activity with subsequent reduction of VO2 and REE. Moreover, dexmedetomidine, has some anti-inflammatory effect by inhibiting the pro-inflammatory cytokines which may cause additional reduction of REE in critically ill patient.
Midazolam is another important sedative that is frequently used in critically-ill patient. Terao et al. found that increasing the depth of sedation using midazolam, decreased oxygen consumption and REE. However, it remains unclear whether the effect of midazolam on REE is related to the drug itself or to the depth of sedation.
There is no direct comparison in the literature between dexmedetomidine and midazolam on REE.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine group | Active comparator | Drug: Dexmedetomidine, Drug: Fentanyl, Device: Indirect calorimetry* Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug. * Group I patients will have dexmedetomidine (0.075 µg.kg-1.mL-1). Dexmedetomidine infusion will be started at 0.15 µg.kg-1.hr-1 (2 mL.hr-1) and will be adjusted by 0.15 µg.kg-1.h-1 increments to a maximum of 0.75 µg/kg/h (10 ml.h-1) * Intervention: indirect calorimetry |
| midazolam group | Placebo comparator | Drug: Midazolam, Drug: Fentanyl, Device: Indirect calorimetry* Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug. * Group II patients will have midazolam (0.5 mg.mL-1). Midazolam will be started at 1 mg.h-1 (2 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (10 mL.h-1). All infusions will be adjusted by increments of 2 mL.hr-1 to maintain blinding. Patients in either group not adequately sedated by the maximum infusion rate of the study medication will receive a bolus dose of fentanyl 0.5 µg.kg-1. * Intervention: indirect calorimetry |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- The study will be designed to recruit 30 critically-ill patients who will be admitted to the surgical ICU for ventilatory support and will be expected to continue for 2 days or longer.
Key exclusion criteria (14 listed)
- Age < 18 years old.
- Pregnant patient.
- Serious central nervous system pathologies (traumatic brain injury, acute stroke, uncontrolled seizures).
- Patient who will require fraction of inspired oxygen more than 0.6.
- Air leak from the chest tube.
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 |
|---|---|---|
| DexmedetomidineAlso: PrecedexThe drug will be administered for sedation and its effect on basal metabolic rate will be investigated | Drug | Dexmedetomidine group |
| MidazolamAlso: dormicumThe drug will be administered for sedation and its effect on basal metabolic rate will be investigated | Drug | midazolam group |
| FentanylThe drug will be administered in both groups | Drug | Dexmedetomidine group, midazolam group |
| Indirect calorimetryAlso: CalorimetryThe device will be used for measurement of basal metabolic rate | Device | Dexmedetomidine group, midazolam group |
Primary outcome
Change in Resting energy expenditure after drug administration
Time frame: The first baseline measurement will be taken before drug administration. The second measurement will be taken 24 hours after drug infusion.
Resting energy expenditure will be measured using indirect calorimetry via metabolic module on General Electric ventilator
10 secondary outcomes
Heart rate
Time frame: 24 hours
arterial blood pressure
Time frame: 24 hours
Richmond agitation and sedation scale
Time frame: 24 hours
Plasma interleukin-1β level
Time frame: 24 hours
Tumor necrosis factor-α plasma concentration
Time frame: 24 hours
partial pressure of oxygen in arterial blood
Time frame: 24 hours
VO2
Time frame: 24 hours
VCO2
Time frame: 24 hours
end-tidal co2
Time frame: 24 hours
cardiac output
Time frame: 24 hours
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 27 Mar 2018.
- Background: PubMed 19327188Walker RN, Heuberger RA. Predictive equations for energy needs for the critically ill. Respir Care. 2009 Apr;54(4):509-21.
- Background: PubMed 14758147Rubinson L, Diette GB, Song X, Brower RG, Krishnan JA. Low caloric intake is associated with nosocomial bloodstream infections in patients in the medical intensive care unit. Crit Care Med. 2004 Feb;32(2):350-7. doi: 10.1097/01.CCM.0000089641.06306.68.
- Background: PubMed 6794409Covelli HD, Black JW, Olsen MS, Beekman JF. Respiratory failure precipitated by high carbohydrate loads. Ann Intern Med. 1981 Nov;95(5):579-81. doi: 10.7326/0003-4819-95-5-579.
- Background: PubMed 11288413Fung EB. Estimating energy expenditure in critically ill adults and children. AACN Clin Issues. 2000 Nov;11(4):480-97. doi: 10.1097/00044067-200011000-00002.
- Individual participant dataSharing planned: Undecided
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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.
Mohamed Abdulatif, Professor study chair
Professor and member of research committee of anesthesia department
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexmedetomidine, Midazolam and Fentanyl in people with Mechanical Ventilation and Dexmedetomidine, run by Cairo University at 1 site in Egypt.
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 14 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 27 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Change in Resting energy expenditure after drug administration (time frame: The first baseline measurement will be taken before drug administration. The second measurement will be taken 24 hours after drug infusion.). 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 NCT03030911, which also lists 4 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 27 Mar 2018.