Trial Outcomes & Findings for Role of Levothyroxine Supplementation in Delayed Recovery Following Cardiac Surgery (NCT NCT06660823)
NCT ID: NCT06660823
Last Updated: 2025-08-17
Results Overview
The Glasgow Coma Scale (GCS) assesses conscious level through three components: Eye response (scored 1-4): 4: Opens eyes spontaneously 3: Opens eyes to verbal command 2: Opens eyes to pain 1: No eye opening Verbal response (scored 1-5): 5: Oriented and converses 4: Confused 3: Inappropriate words 2: Incomprehensible sounds 1: No verbal response Motor response (scored 1-6): 6: Obeys commands 5: Localizes to pain 4: Withdraws from pain 3: Abnormal flexion (decorticate) 2: Abnormal extension (decerebrate) 1: No motor response The total GCS score ranges from 3 (worst) to 15 (best), with higher scores indicating better neurological function. The primary outcome is the change in total GCS score from baseline (48 hours postoperatively, before intervention) to ICU discharge.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
70 participants
Primary outcome timeframe
From intervention initiation (48 hours postoperatively) to ICU discharge, up to 1 month postoperatively. (i.e., within 28 days after baseline).
Results posted on
2025-08-17
Participant Flow
Participant milestones
| Measure |
Group A (Study Group)
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
35
|
|
Overall Study
COMPLETED
|
35
|
35
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Group A (Study Group)
n=35 Participants
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
n=35 Participants
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.94 years
STANDARD_DEVIATION 15.33 • n=35 Participants
|
57.57 years
STANDARD_DEVIATION 7.12 • n=35 Participants
|
55.76 years
STANDARD_DEVIATION 12.01 • n=70 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=35 Participants
|
11 Participants
n=35 Participants
|
28 Participants
n=70 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=35 Participants
|
24 Participants
n=35 Participants
|
42 Participants
n=70 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
PRIMARY outcome
Timeframe: From intervention initiation (48 hours postoperatively) to ICU discharge, up to 1 month postoperatively. (i.e., within 28 days after baseline).The Glasgow Coma Scale (GCS) assesses conscious level through three components: Eye response (scored 1-4): 4: Opens eyes spontaneously 3: Opens eyes to verbal command 2: Opens eyes to pain 1: No eye opening Verbal response (scored 1-5): 5: Oriented and converses 4: Confused 3: Inappropriate words 2: Incomprehensible sounds 1: No verbal response Motor response (scored 1-6): 6: Obeys commands 5: Localizes to pain 4: Withdraws from pain 3: Abnormal flexion (decorticate) 2: Abnormal extension (decerebrate) 1: No motor response The total GCS score ranges from 3 (worst) to 15 (best), with higher scores indicating better neurological function. The primary outcome is the change in total GCS score from baseline (48 hours postoperatively, before intervention) to ICU discharge.
Outcome measures
| Measure |
Group A (Study Group)
n=35 Participants
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
n=35 Participants
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
|---|---|---|
|
Change in Glasgow Coma Scale (GCS) From Intervention Initiation to ICU Discharge (Δ)
|
6.65 Score on a scale
Standard Deviation 3.60
|
2.69 Score on a scale
Standard Deviation 0.64
|
SECONDARY outcome
Timeframe: From surgery completion until extubation (assessed for ≤30 days postoperatively).Population: All 70 participants included in intention-to-treat analysis. Duration calculated for survivors until extubation; deceased patients contributed ventilation hours until death.
Total time (in hours) from initiation of mechanical ventilation postoperatively until successful extubation, including time before and after study intervention.
Outcome measures
| Measure |
Group A (Study Group)
n=35 Participants
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
n=35 Participants
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
|---|---|---|
|
Total Duration of Mechanical Ventilation
|
130.40 hours
Standard Deviation 75.74
|
142.14 hours
Standard Deviation 41.37
|
SECONDARY outcome
Timeframe: From ICU admission until discharge/death (assessed for ≤30 days postoperatively).Population: All 70 participants included in intention-to-treat analysis. Duration calculated for: Survivors: Until ICU discharge Non-survivors: Until death in ICU
Total time (in days) from ICU admission after cardiac surgery until discharge from ICU or death.
Outcome measures
| Measure |
Group A (Study Group)
n=35 Participants
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
n=35 Participants
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
|---|---|---|
|
Duration of Intensive Care Unit (ICU) Stay
|
9.03 days
Standard Deviation 5.42
|
7.51 days
Standard Deviation 1.80
|
SECONDARY outcome
Timeframe: 30 daysThe total hospital stay will be recorded in days and compared between both groups.
Outcome measures
| Measure |
Group A (Study Group)
n=35 Participants
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
n=35 Participants
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
|---|---|---|
|
Total Hospital Stay Stay.
|
13.06 days
Standard Deviation 4.49
|
10.29 days
Standard Deviation 3.48
|
SECONDARY outcome
Timeframe: From ICU admission until discontinuation of inotropic support or ICU discharge (assessed daily for ≤30 days).Population: All 70 participants were included in the analysis per intention-to-treat. Average infusion rates were calculated based on the total dose administered, patient weight, and total duration of infusion during the ICU stay.
Average infusion rate (in ng/kg/min) of norepinephrine and epinephrine administered during ICU stay. Calculated as total dose (ng) divided by patient weight (kg) and total infusion duration (minutes). Does not include intraoperative inotropic support.
Outcome measures
| Measure |
Group A (Study Group)
n=35 Participants
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
n=35 Participants
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
|---|---|---|
|
Average Inotropic Support Infusion Rate in ICU
Nor Epinephrine
|
79.60 ng/kg/min
Standard Deviation 51.60
|
135.86 ng/kg/min
Standard Deviation 93.98
|
|
Average Inotropic Support Infusion Rate in ICU
Epinephrine
|
83.70 ng/kg/min
Standard Deviation 40.21
|
137.93 ng/kg/min
Standard Deviation 78.26
|
SECONDARY outcome
Timeframe: Preoperative assessment: Within 24 hours before surgery Postoperative assessment: At ICU discharge (≤30 days postoperatively)Population: All 70 participants included in intention-to-treat analysis. Echocardiography performed by blinded cardiologists per institutional protocols.
Absolute change in left ventricular ejection fraction (LVEF) measured by transthoracic echocardiography, calculated as: Δ EF = Postoperative EF \- Preoperative EF Δ EF * Postoperative EF-Preoperative EF Negative values indicate decline in cardiac function.
Outcome measures
| Measure |
Group A (Study Group)
n=35 Participants
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
n=35 Participants
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
|---|---|---|
|
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to ICU Discharge
|
-6.15 Percentage points of ejection fraction
Standard Deviation 4.32
|
-19.14 Percentage points of ejection fraction
Standard Deviation 10.21
|
SECONDARY outcome
Timeframe: From ICU admission until discharge or death (≤30 days postoperatively).Population: All 70 participants included in intention-to-treat analysis. Arrhythmias diagnosed by blinded cardiologists using: Continuous ECG monitoring 12-lead ECG for confirmation
Incidence of new-onset supraventricular arrhythmias (atrial fibrillation, atrial flutter, or supraventricular tachycardia) confirmed by 12-lead ECG during ICU stay. Excludes pre-existing arrhythmias.
Outcome measures
| Measure |
Group A (Study Group)
n=35 Participants
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
n=35 Participants
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
|---|---|---|
|
Number of Participants With New-onset Supraventricular Arrhythmia
|
1 participants
|
13 participants
|
Adverse Events
Group A (Study Group)
Serious events: 1 serious events
Other events: 0 other events
Deaths: 5 deaths
Group B (Control)
Serious events: 13 serious events
Other events: 0 other events
Deaths: 16 deaths
Serious adverse events
| Measure |
Group A (Study Group)
n=35 participants at risk
group A will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI
L-thyroxine: Patients who show signs of delayed recovery defined as either prolonged ventilation for 48 hours or delayed conscious level recovery for 48 hours despite exclusion of muscle relaxants and/or sedative drugs. Those patients will undergo CT brain, CT chest and neurological examination to exclude structural damage as per institutional protocols. Also, metabolic profile screening including full kidney function, full liver function, electrolyte to exclude correctable metabolic abnormalities. and thyroid profile (TSH, free T3, free T4) sick euthyroid patients who are having normal FreeT3, normal Free T4, low TSH and low level of free T3 or freeT4 will be included in the study according lab reference.Daily assessment of conscious level according to Glasgow Coma Scale (GCS) and spontaneous breathing trial by ICU consultant (the investigator) till ICU discharge.
Patients will receive levothyroxine via Ryle, dose of 25 to 50 ug/ day according to BMI.
|
Group B (Control)
n=35 participants at risk
group B will receive placebo in form of inert starch tablet
Placebo Oral Tablet: patients will receive placebo oral tablet
|
|---|---|---|
|
Cardiac disorders
Arrhythmias
|
2.9%
1/35 • Number of events 1 • 30 day
adverse events were already defined as all cause mortality and arrhythmias
|
37.1%
13/35 • Number of events 13 • 30 day
adverse events were already defined as all cause mortality and arrhythmias
|
Other adverse events
Adverse event data not reported
Additional Information
Dr.Mohammed Abd Al Jawad,Professor of cardiac surgery
Ain Shams University
Phone: +201111219461
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place