Study To Investigate The Effectiveness Of Pregabalin For Management Of Patients Undergoing Total Hip Replacement

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00905437
• Collaborator: (none)
• Enrollment: 72
• Locations: 7
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is the investigate if pregabalin started a day before surgery and continued for 14 days post-operatively can reduce post-operative pain, relieve pre- and post-operative anxiety and sleep disturbances.

Condition or Disease	Intervention/Treatment	Phase
Pain, Perioperative	Drug: Placebo; Drug: Pregabalin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Randomized Double-Blind, Multi-Center Study Of Efficacy And Tolerability Of Pregabalin Versus Placebo As An Adjunct To Standard Of Care For Perioperative Management Of Patients Undergoing Total Hip Arthroplasty
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo as an adjunct to standard of care	Drug: Placebo; Placebo as an adjunct to standard of care
Active Comparator: Pregabalin Pregabalin as an adjunct to standard of care	Drug: Pregabalin; 75 mg BD for 14 days

Outcome Measures

Primary Outcome Measures

1. Mean Pain on Movement Score [Every 12 hours from Day 1 to Day 5 post-surgery]

   Mean pain on movement score was defined as the mean of the pain on movement score over Days 1 to 5 post-surgery. Pain experienced by participant during passive flexion through 90 degree and passive abduction through 30 degree at operated hip joint was evaluated on a scale of 0 to 10 where, 0= no pain and 10= worst possible pain.

Secondary Outcome Measures

1. Mean Daily Pain Score [Day 1 to Day 7, Day 8 to Day 14 post-surgery]

   Mean daily pain score was defined as the mean of daily pain score over Days 1 to 7 and Days 8 to 14 post-surgery. Daily Pain Rating Scale (DPRS): participant rated 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain.

2. Mean Daily Sleep Interference Score [Day 1 to Day 5 post-surgery]

   Mean daily sleep interference score was defined as the mean of daily sleep interference numeric rating scale (NRS) score over Days 1 to 5 post-surgery. Daily Sleep Interference Scale (DSIS): participant rated pain during past 24-hour period on NRS ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep). Higher score indicates a greater level of sleep disturbance. Self-assessment performed daily on awakening prior to taking study medication.

3. Mean Anxiety Visual Analogue Scale (A-VAS) [Day 0 to Day 5 post-surgery]

   Mean anxiety visual analogue scale (VAS) was defined as the mean of VAS score on the day of surgery and over Days 1 to 5 post-surgery. Participants measured their degree of anxiety over past 24 hours on a VAS of 0 to 100, where 0 = not at all anxious to 100 = extremely anxious.

4. Time to Mobilization After Surgery [Day 1 to Day 5 post-surgery]

   Participant was encouraged each day (from Day 3) to attempt walking depending upon the degree of pain on standing. The first day on which the participant was able to walk for 5 steps was the day of mobilization. Median time to mobilization (in hours) was calculated till the day of mobilization.

5. Number of Participants With Rescue Medication Usage [Day 0 to Day 6 post-surgery]

   Rescue medications were used for participants with moderate or severe resting pain. Fentanyl injection (25 microgram [mcg] intravenous bolus to a maximum dose of 3 milliliter/day), paracetamol tablet (15 milligram/kilogram orally to a maximum dose of 45 milligram/kilogram/day) were used as rescue medications.

6. Number of Participants With Neuropathic Pain [Day 90, Day 180 post-surgery]

   ID Pain questionnaire was used to assess neuropathic pain. 6 items questionnaire, did pain feel like: (1)pins and needles (2)hot/burning (3)numb (4)electrical shocks (5)is pain made worse with touch of clothing or bed sheets (6)is pain limited to your joints. "Yes" response to questions 1-5 were scored as 1, while a "yes" response to question 6 was scored as -1. "No" response were scored as 0. Overall score range -1 to 5.Higher score more indicative of pain with a neuropathic component. Number of participants with score 2 or more (which indicated nerve pain) were reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient is undergoing a routine (i.e., expected to be uncomplicated) total primary or secondary hip replacement surgery performed under a standardized regimen of spinal anesthesia, and is expected to experience moderate to severe post-surgical pain in the absence of post-operative analgesia

Exclusion Criteria:

• The patient is undergoing a revision to a previous hip replacement procedure, hip replacement procedure further to a road traffic accident with multiple injuries, or a procedure expected to last longer than 4 hours

• The patient has a history of uncontrolled chronic disease or a concurrent clinically significant illness or medical condition, which in the Investigator's opinion, would contraindicate study participation or confound interpretation of the results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Hyderabad	Andhra Pradesh	India	500 033
2	Pfizer Investigational Site	Ahmedabad	Gujarat	India	380 015
3	Pfizer Investigational Site	Bangalore	Karnataka	India	560 076
4	Pfizer Investigational Site	Kanpur	Uttar Pradesh,	India	208 001
5	Pfizer Investigational Site	Kanpur	Uttar Pradesh	India	208 002
6	Pfizer Investigational Site	Kolkata	West Bengal	India	700 054
7	Pfizer Investigational Site	New Delhi		India	110 017

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00905437
• Other Study ID Numbers: A0081229
• First Posted: May 20, 2009
• Last Update Posted: Jan 28, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: perioperative; pregabalin; total hip replacement; post-operative pain
• Additional relevant MeSH terms: Pregabalin

Study Results

Participant Flow

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.	Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.
Period Title: Overall Study
STARTED	35	37
COMPLETED	27	27
NOT COMPLETED	8	10

Baseline Characteristics

Arm/Group Title	Pregabalin	Placebo	Total
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.	Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.	Total of all reporting groups
Overall Participants	35	37	72
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.1 (13.5)	48.9 (13.3)	48.0 (13.3)
Sex: Female, Male (Count of Participants)
Female	15 42.9%	20 54.1%	35 48.6%
Male	20 57.1%	17 45.9%	37 51.4%

Outcome Measures

1. Primary Outcome

Title	Mean Pain on Movement Score
Description	Mean pain on movement score was defined as the mean of the pain on movement score over Days 1 to 5 post-surgery. Pain experienced by participant during passive flexion through 90 degree and passive abduction through 30 degree at operated hip joint was evaluated on a scale of 0 to 10 where, 0= no pain and 10= worst possible pain.
Time Frame	Every 12 hours from Day 1 to Day 5 post-surgery

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat (MITT) population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.	Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.
Measure Participants	27	30
Mean (Standard Error) [Units on a scale]	4.0 (0.23)	3.9 (0.26)

2. Secondary Outcome

Title	Mean Daily Pain Score
Description	Mean daily pain score was defined as the mean of daily pain score over Days 1 to 7 and Days 8 to 14 post-surgery. Daily Pain Rating Scale (DPRS): participant rated 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain.
Time Frame	Day 1 to Day 7, Day 8 to Day 14 post-surgery

Outcome Measure Data

Analysis Population Description

MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure. 'n' signifies participants who were evaluable for this measure at specified time-point for each arm.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.	Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.
Measure Participants	27	30
Days 1 to 7 (n=27,30)	2.6 (0.23)	2.6 (0.24)
Days 8 to 14 (n=26,27)	1.8 (0.25)	1.4 (0.25)

3. Secondary Outcome

Title	Mean Daily Sleep Interference Score
Description	Mean daily sleep interference score was defined as the mean of daily sleep interference numeric rating scale (NRS) score over Days 1 to 5 post-surgery. Daily Sleep Interference Scale (DSIS): participant rated pain during past 24-hour period on NRS ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep). Higher score indicates a greater level of sleep disturbance. Self-assessment performed daily on awakening prior to taking study medication.
Time Frame	Day 1 to Day 5 post-surgery

Outcome Measure Data

Analysis Population Description

MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.	Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.
Measure Participants	27	30
Mean (Standard Error) [Units on a scale]	2.6 (0.34)	3.1 (0.29)

4. Secondary Outcome

Title	Mean Anxiety Visual Analogue Scale (A-VAS)
Description	Mean anxiety visual analogue scale (VAS) was defined as the mean of VAS score on the day of surgery and over Days 1 to 5 post-surgery. Participants measured their degree of anxiety over past 24 hours on a VAS of 0 to 100, where 0 = not at all anxious to 100 = extremely anxious.
Time Frame	Day 0 to Day 5 post-surgery

Outcome Measure Data

Analysis Population Description

MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.	Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.
Measure Participants	32	36
Mean (Standard Error) [Units on a scale]	23.3 (3.33)	24.7 (2.88)

5. Secondary Outcome

Title	Time to Mobilization After Surgery
Description	Participant was encouraged each day (from Day 3) to attempt walking depending upon the degree of pain on standing. The first day on which the participant was able to walk for 5 steps was the day of mobilization. Median time to mobilization (in hours) was calculated till the day of mobilization.
Time Frame	Day 1 to Day 5 post-surgery

Outcome Measure Data

Analysis Population Description

MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.	Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.
Measure Participants	33	35
Median (Inter-Quartile Range) [hours]	72.500	52.417

6. Secondary Outcome

Title	Number of Participants With Rescue Medication Usage
Description	Rescue medications were used for participants with moderate or severe resting pain. Fentanyl injection (25 microgram [mcg] intravenous bolus to a maximum dose of 3 milliliter/day), paracetamol tablet (15 milligram/kilogram orally to a maximum dose of 45 milligram/kilogram/day) were used as rescue medications.
Time Frame	Day 0 to Day 6 post-surgery

Outcome Measure Data

Analysis Population Description

MITT population included all randomized participants who had at least taken pre-surgery study medication and had no surgical complications.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.	Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.
Measure Participants	33	36
Number [participants]	17 48.6%	25 67.6%

7. Secondary Outcome

Title	Number of Participants With Neuropathic Pain
Description	ID Pain questionnaire was used to assess neuropathic pain. 6 items questionnaire, did pain feel like: (1)pins and needles (2)hot/burning (3)numb (4)electrical shocks (5)is pain made worse with touch of clothing or bed sheets (6)is pain limited to your joints. "Yes" response to questions 1-5 were scored as 1, while a "yes" response to question 6 was scored as -1. "No" response were scored as 0. Overall score range -1 to 5.Higher score more indicative of pain with a neuropathic component. Number of participants with score 2 or more (which indicated nerve pain) were reported.
Time Frame	Day 90, Day 180 post-surgery

Outcome Measure Data

Analysis Population Description

Data was not analyzed as the intended sample size was not met, and the reported numbers from the final set were not sufficient for a meaningful analysis.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.	Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Pregabalin		Placebo
Arm/Group Description	Pregabalin 75 milligram (mg) capsule orally twice daily for 14 days.		Placebo matched to pregabalin 75 mg capsule orally twice daily for 14 days.
All Cause Mortality
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/35 (5.7%)		0/37 (0%)
Investigations
Oxygen saturation decreased	1/35 (2.9%)		0/37 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/35 (2.9%)		0/37 (0%)
Vascular disorders
Hypotension	1/35 (2.9%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/35 (65.7%)		22/37 (59.5%)
Gastrointestinal disorders
Abdominal pain	0/35 (0%)		1/37 (2.7%)
Constipation	3/35 (8.6%)		3/37 (8.1%)
Diarrhoea	1/35 (2.9%)		1/37 (2.7%)
Dry mouth	1/35 (2.9%)		0/37 (0%)
Dyspepsia	0/35 (0%)		1/37 (2.7%)
Hyperchlorhydria	0/35 (0%)		1/37 (2.7%)
Nausea	1/35 (2.9%)		1/37 (2.7%)
Vomiting	2/35 (5.7%)		3/37 (8.1%)
General disorders
Pain	2/35 (5.7%)		2/37 (5.4%)
Pyrexia	16/35 (45.7%)		10/37 (27%)
Immune system disorders
Drug hypersensitivity	0/35 (0%)		1/37 (2.7%)
Infections and infestations
Orchitis	0/35 (0%)		1/37 (2.7%)
Urinary tract infection	0/35 (0%)		1/37 (2.7%)
Urinary retention postoperative	0/35 (0%)		1/37 (2.7%)
Injury, poisoning and procedural complications
Post procedural haemorrhage	0/35 (0%)		1/37 (2.7%)
Procedural pain	1/35 (2.9%)		1/37 (2.7%)
Investigations
Haemoglobin decreased	0/35 (0%)		3/37 (8.1%)
Musculoskeletal and connective tissue disorders
Back pain	1/35 (2.9%)		2/37 (5.4%)
Musculoskeletal stiffness	0/35 (0%)		1/37 (2.7%)
Nervous system disorders
Headache	2/35 (5.7%)		1/37 (2.7%)
Somnolence	1/35 (2.9%)		0/37 (0%)
Psychiatric disorders
Restlessness	0/35 (0%)		1/37 (2.7%)
Renal and urinary disorders
Bladder disorder	1/35 (2.9%)		0/37 (0%)
Bladder pain	0/35 (0%)		1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Cough	3/35 (8.6%)		1/37 (2.7%)
Oropharyngeal pain	0/35 (0%)		1/37 (2.7%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/35 (2.9%)		0/37 (0%)
Pruritus	0/35 (0%)		1/37 (2.7%)
Vascular disorders
Hypertension	1/35 (2.9%)		1/37 (2.7%)
Hypotension	2/35 (5.7%)		2/37 (5.4%)

Limitations/Caveats

As the enrollment rate was very low, the study was prematurely terminated. The number of enrolled participants was too low for meaningful formal statistical conclusions.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.