Trial Outcomes & Findings for Effect of Nitrous Oxide in Treating Neuropathic Pain: A Study in Chronic Low Back Pain Patients (NCT NCT01172600)

Results Overview

10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to the 3 month follow-up.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

78 participants

Primary outcome timeframe

At baseline (before 1st block) and 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks)

Results posted on

2016-10-17

Participant Flow

Participant milestones

Participant milestones
Measure	Entonox Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Overall Study STARTED	39	39
Overall Study COMPLETED	39	39
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Nitrous Oxide in Treating Neuropathic Pain: A Study in Chronic Low Back Pain Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entonox n=39 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=39 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Total n=78 Participants Total of all reporting groups
Age, Continuous	70 years STANDARD_DEVIATION 20 • n=5 Participants	73 years STANDARD_DEVIATION 16 • n=7 Participants	71 years STANDARD_DEVIATION 18 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	21 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	18 Participants n=7 Participants	40 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	27 participants n=5 Participants	27 participants n=7 Participants	54 participants n=5 Participants
Race/Ethnicity, Customized African American	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants
Body mass index	30 kg/m2 n=5 Participants	28 kg/m2 n=7 Participants	30 kg/m2 n=5 Participants
American Society of Anesthesiologists physical status I: A normal healthy patient	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
American Society of Anesthesiologists physical status II: A patient with mild systemic disease	30 participants n=5 Participants	27 participants n=7 Participants	57 participants n=5 Participants
American Society of Anesthesiologists physical status III: A patient with severe systemic disease	0 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants
Smoking status Current Smoker	10 participants n=5 Participants	9 participants n=7 Participants	19 participants n=5 Participants
Smoking status Previously quit	15 participants n=5 Participants	12 participants n=7 Participants	27 participants n=5 Participants
Smoking status Never smoked	14 participants n=5 Participants	18 participants n=7 Participants	32 participants n=5 Participants

PRIMARY outcome

Timeframe: At baseline (before 1st block) and 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks)

Population: For 10 patients with missing VAS at 3 month follow up: 5 patients who had 2nd or 3rd epidural block, we assigned the last VAS observation (i.e., from VAS before 2nd or 3rd block to 3 month follow-up); and for 5 patients who only had 1st epidural, we assigned the worst VAS (10) for Entonox patients and the best VAS (0) for Oxygen patients.

10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to the 3 month follow-up.

Outcome measures

Outcome measures
Measure	Entonox n=39 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=39 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Change in VAS Pain Score From Baseline to 3 Month Follow-up	-1.6 units on a scale Standard Deviation 3.0	-1.2 units on a scale Standard Deviation 2.6

PRIMARY outcome

Timeframe: At baseline (before 1st block) and before the 2nd block, typically at 1 month from baseline

Population: 10 patients in the Entonox group and 11 patients in the Oxygen group did not receive the 2nd block treatment

10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to before the 2nd block.

Outcome measures

Outcome measures
Measure	Entonox n=29 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=28 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Change in VAS Pain Score From Baseline to Before 2nd Block	-0.6 units on a scale Standard Deviation 1.7	-0.4 units on a scale Standard Deviation 2.1

PRIMARY outcome

Timeframe: At baseline (before 1st block) and before the 3rd block, typically at 2 months from baseline

Population: 21 patients in the Entonox group and 26 patients in the Oxygen group did not receive the 2nd block treatment

10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to before the 3rd block

Outcome measures

Outcome measures
Measure	Entonox n=18 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=13 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Change in VAS Pain Score From Baseline to Before 3rd Block	-2.1 units on a scale Standard Deviation 3.0	-0.5 units on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: At baseline (before 1st block) and before the 2nd block, typically at 1 month from baseline

Population: 10 Entonox patients and 11 Oxygen patients did not receive 2nd block.

Oswestry score ranges from 0% to 100%, which measures % of disability. The outcome is change in the Oswestry score from baseline (before 1st block) to before 2nd block.

Outcome measures

Outcome measures
Measure	Entonox n=29 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=28 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Change in Oswestry Score (% of Disability) From Baseline to 2nd Block	-7 absolute percentage Standard Deviation 14	-6 absolute percentage Standard Deviation 14

SECONDARY outcome

Timeframe: At baseline (before 1st block) and before the 3rd block, typically at 2 months from baseline

Population: 21 Entonox patients and 26 Oxygen patients did not receive 3rd block.

Oswestry score ranges from 0% to 100%, which measures % of disability. The outcome is change in the Oswestry score from baseline (before 1st block) to before 3rd block.

Outcome measures

Outcome measures
Measure	Entonox n=18 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=13 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Change in Oswestry Score (% of Disability) From Baseline to 3rd Block	-10 absolute percentage Standard Deviation 13	-7 absolute percentage Standard Deviation 18

SECONDARY outcome

Timeframe: At baseline (before 1st block) and 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks)

Population: 5 patients in each group were lost follow-up.

Oswestry score ranges from 0% to 100%, which measures % of disability. The outcome is change in the Oswestry score from baseline (before 1st block) to 3 months follow-up.

Outcome measures

Outcome measures
Measure	Entonox n=34 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=34 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Change in Oswestry Score (% of Disability) From Baseline to 3 Months Follow-up	-11 absolute percentage Standard Deviation 19	-6 absolute percentage Standard Deviation 21

SECONDARY outcome

Timeframe: 2nd block, typically at 1 month from baseline

Population: 10 Entonox patients and 11 Oxygen patients did not receive 2nd block.

Outcome measures

Outcome measures
Measure	Entonox n=29 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=28 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Usage of Opioids	3 participants	7 participants

SECONDARY outcome

Timeframe: 3rd block, typically at 2 months from baseline

Population: 21 Entonox patients and 26 Oxygen patients did not receive 2nd block.

Outcome measures

Outcome measures
Measure	Entonox n=18 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=13 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Usage of Opioid	3 participants	2 participants

SECONDARY outcome

Timeframe: 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks)

Population: 5 patients in each group were lost follow up.

Outcome measures

Outcome measures
Measure	Entonox n=34 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=34 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Usage of Opioid	6 participants	9 participants

SECONDARY outcome

Timeframe: baseline - before 1st block

Population: Blood sample was not collected for 5 Entonox patients and 1 Oxygen patients.

BIOMARKERS: IL-1β, IL-6, IL-10, 1L-17A, IFN-γ, and TNF-α

Outcome measures

Outcome measures
Measure	Entonox n=34 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=38 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Biomarkers IL-1β	206 pg/ml Interval 88.0 to 372.0	140 pg/ml Interval 72.0 to 347.0
Biomarkers IL-6	226 pg/ml Interval 126.0 to 458.0	198 pg/ml Interval 118.0 to 579.0
Biomarkers IL-10	174 pg/ml Interval 130.0 to 294.0	176 pg/ml Interval 143.0 to 397.0
Biomarkers IL-17A	146 pg/ml Interval 104.0 to 256.0	137 pg/ml Interval 105.0 to 183.0
Biomarkers IFN-γ	93 pg/ml Interval 77.0 to 176.0	85 pg/ml Interval 73.0 to 182.0
Biomarkers TNF-α	13 pg/ml Interval 7.0 to 24.0	9 pg/ml Interval 5.0 to 24.0

SECONDARY outcome

Timeframe: before 2nd block, typically at 1 month from baseline

Population: 10 Entonox patients and 11 Oxygen patients did not come for 2nd block. Among patients came for the 2nd block, blood sample was not collected in 9 Entonox patients and 6 Oxygen patients.

BIOMARKERS: IL-1β, IL-6, IL-10, 1L-17A, IFN-γ, and TNF-α

Outcome measures

Outcome measures
Measure	Entonox n=20 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=22 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Biomarkers IL-1β	128 pg/ml Interval 64.0 to 289.0	100 pg/ml Interval 57.0 to 728.0
Biomarkers IL-6	224 pg/ml Interval 99.0 to 321.0	127 pg/ml Interval 99.0 to 797.0
Biomarkers IL-10	142 pg/ml Interval 102.0 to 305.0	163 pg/ml Interval 122.0 to 493.0
Biomarkers IL-17A	146 pg/ml Interval 114.0 to 285.0	128 pg/ml Interval 99.0 to 198.0
Biomarkers IFN-γ	124 pg/ml Interval 73.0 to 337.0	79 pg/ml Interval 63.0 to 129.0
Biomarkers TNF-α	10 pg/ml Interval 4.0 to 21.0	10 pg/ml Interval 3.0 to 23.0

SECONDARY outcome

Timeframe: before 3rd block, typically at 2 months from baseline

Population: 21 Entonox patients and 26 Oxygen patients did come for the 3rd block. Among the patients who came for the 3rd block, blood sample was not collected in 5 Entonox patients and 1 Oxygen patient.

BIOMARKERS: IL-1β, IL-6, IL-10, 1L-17A, IFN-γ, and TNF-α

Outcome measures

Outcome measures
Measure	Entonox n=13 Participants Patients will receive inhaled Entonox along with the interventional block they are scheduled. Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.	Oxygen n=12 Participants Patients will receive inhaled oxygen along with the interventional block they are scheduled. Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Biomarkers IL-1β	120 pg/ml Interval 64.0 to 231.0	113 pg/ml Interval 99.0 to 316.0
Biomarkers IL-6	110 pg/ml Interval 90.0 to 258.0	239 pg/ml Interval 142.0 to 432.0
Biomarkers IL-10	170 pg/ml Interval 125.0 to 301.0	244 pg/ml Interval 146.0 to 651.0
Biomarkers IL-17A	153 pg/ml Interval 99.0 to 195.0	140 pg/ml Interval 123.0 to 186.0
Biomarkers IFN-γ	97 pg/ml Interval 69.0 to 138.0	88 pg/ml Interval 73.0 to 120.0
Biomarkers TNF-α	5 pg/ml Interval 4.0 to 9.0	11 pg/ml Interval 7.0 to 13.0

SECONDARY outcome

Timeframe: 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks)

Population: No blood sample was planned to be collected.

BIOMARKERS: IL-1β, IL-6, IL-10, 1L-17A, IFN-γ, and TNF-α

Outcome measures

Outcome data not reported

Adverse Events

Entonox

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Oxygen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Alparslan Turan, MD

Cleveland Clinic

Phone: 216-445-9857

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place