Safety and Efficacy of the Addition of Morphine Chloride to a Low Dose of Bupivacaine as Intradural Anaesthetic for the Removal Surgery of the Hemorrhoids

• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Principe de Asturias (Other)
• Overall Status: Completed
• CT.gov ID: NCT02046772
• Collaborator: Spanish Agency of Medicines and Health Products (Other), Spanish Health Ministry (Other)
• Enrollment: 63
• Locations: 2
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 31.5
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

A single blind, randomized, with blinded evaluation by third parties clinical trial is carried out to assess the analgesic efficay of the addition of morphine chloride to a low dose solution of spinal local anaesthetic compared to a standard dose spinal anaesthetic in the haemorrhoid surgery.

The objective of this clinical trial is to assess if the experimental treatment is as efficacy as the standard treatment in the anesthetic and analgesic effects with less side effects, greater and earlier mobility after surgery and shortened the hospitalization.

Condition or Disease	Intervention/Treatment	Phase
Surgical Remove of Hemorrhoids	Drug: Bupivacaine low dose; Drug: Bupivacaine standard dose; Drug: Morphine Chloride	Phase 4

Detailed Description

DESIGN OF THE TRIAL:

A multicentre, randomized, single-blind, with masked evaluationby third parties clinical trial.

The Clinical Pharmacology Unit will perform a permuted blocks randomization scheme for each of the two hospitals participating in the trial. The result of this randomization will be kept in this unit and will not be accessible to investigators. Investigators will receive a series of opaque sealed envelopes with a number corresponding to the order of entry of the patients into the trial. When the patient is in the operating room, investigators must open the envelope which contains the group of treatment assigned to that patient. The patient will not know in which intervention group is included. Investigator who performs the spinal puncture and investigator who collects the data and performs the evaluation will no be the same person. This will allow a blind evaluation.

OBJECTIVES:

Main objective:

To evaluate whether the addition of morphine chloride to a low dose solution of local intradural anaesthetic in patients undergoing hemorrhoids surgery produces an anaesthetic efficacy comparable to that produced by a standard dose of local intradural anaesthetic and an improvement of postoperative analgesic efficacy.

Secondary objectives:

• Earlier mobilization of the patient.

• Minor adverse effects.

• A shorter hospital stay of the patient.

TREATMENTS:

Two groups of treatment will be formed, experimental and comparator. The experimental group will receive 3mg of Bupivacaine with addition of 50 micrograms of Morphine Chloride.

The comparator group will receive 5 mg of Bupivacaine.

RESCUE TREATMENTS

If necessary before surgery, midazolam will be administered from 0.02 to 0.05 mg / kg intravenous (IV) depending on clinical response and after the patient is set in the surgical position, if necessary, an intravenous infusion of propofol will be administered at 0.5 - 2mg / kg / h. Sedative drugs with analgesic effects as opioids, ketamine, etc, will be avoided to not interfere with the main analgesic study assessment.

After surgery and during the hospitalization stay the rescue analgesia treatment will be administered only on demand. The rescue treatment allowed by protocol will be an intravenous administration of dexketoprofen up to 50 mg / 8 h and if insufficient, a rescue of 3 mg of morphine chloride will be administered. If morphine chloride is received, these patients will be recorded in the case report forms as inefficacy of the treatment. At home, after discharge, patients will receive rescue analgesia with capsules of dexketoprofen 25 mg / 8 h. (up to 75 mg a day).

SAMPLE SIZE:

66 patients ( 33 patients in the experimental group and 33 patients in the control group)

EFFICACY ASSESSMENT

Pain will be assessed using a visual analog scale (VAS from 0 to 10) at the beginning and end of surgery, at the arrival of resuscitation unit, after 10 and 30 minutes after arrival, during hospitalization stay out of the resuscitation unit and daily at home after discharge.

Doses required of rescue analgesia and hospitalization time will be recorded.

SAFETY ASSESSMENT

Basic monitoring as usual will be perfomed in the surgery room. Motor blockage will be assessed using the modified Bromage scale as follows: 1 = complete motor blocking, 2 = able to move feet only, 3 = patient move the feet and bend the knee, 4 = straight leg raises <30 ° or > 30 ° but not against resistance, 5 = lifts leg> 30 ° against resistance. This measure will be made after surgery in the surgery room and at the arrival and at one hour after resuscitation unit admission.

All the Adverse events will be reported.

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Assessment of the Analgesic Efficacy of Morphine Chloride in Addition to a Low Dose Solution of Spinal Anaesthetic in Hemorrhoidectomy Compared to a Standard Dose of Spinal Local Anaesthetic. Simple Blind, Randomized, With Blinded Evaluation by Third Parties Clinical Trial.
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bupivacaine + Morphine Chloride People in this arm will receive treatment with morphine chloride in addition to a low dose solution of the local intradural anaesthetic bupivacaine.	Drug: Bupivacaine low dose; A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural; Drug: Morphine Chloride; A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural
Active Comparator: Bupivacaine standard dose People in this arm will receive treatment with the standard dose of the local intradural anaesthetic bupivacaine	Drug: Bupivacaine standard dose; Single intradural standard dose of bupivacaine

Outcome Measures

Primary Outcome Measures

1. Measurement of Time to Start the Anaesthetic Effect [First 20 minutes between administration and beginning of surgery]

   To compare whether the addition of morphine chloride to a low dose intradural solution of the local anaesthetic bupivacaine is as effective as an administration of a single dose of bupivacaine.

2. Measurement of the Analgesic Effect After Surgery by VAS From 0 to 10, Where 0 is no Pain and 10 is the Worst Pain Imaginable. [Up to 72 hours from the end of the surgery in the hospital stay and during the next 7 days at home, after discharge]

   To compare whether the addition of morphine chloride to a low dose solution of bupivacaine and improves the analgesic treatment than a single administration of bupivacaine.

Secondary Outcome Measures

1. Greater and Earlier Mobilization Measured by Bromage Scale. [During the first 24 hours after surgery and at the entry and exit of the resuscitation unit]

   To assess whether the administration of morphine chloride in addition to a low dose solution of local intradural anaesthetic (bupivacaine) improves the mobilization of the patients after surgery more than the single intradural administration of bupivacaine. Total Score in the Bromage Scale goes from 1 to 5, where: 1: complete motor blocking - 2: capable to move the feet - 3: moves the feet and bends the knee - 4: raise the leg straight more or less than 30 degrees but no against resistance - 5: raise the leg straight more than 30 degrees against resistance (no motor blocking)

2. Number of Adverse Events [Up to 72 hours from the intervention and the hopitalary stay and during the next 7 days after discharge]

   To assess if the experimental treatment causes less, equal or more adverse events than the comparator treatment.

3. Time of Hospitalization [Up to 72 hours after the intervention]

   To see if the hospitalization time is shortened or not by the experimental treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients undergoing hemorrhoidectomy.

• Age between 18 and 64.

• Both gender

• ASA I to III.

• With indication for spinal block.

• People capable to grant the informed consent.

Exclusion Criteria:

• Patients with allergies to the study drugs.

• Patients with any contraindication for performing a spinal technique (coagulation disorders, fever, intracraneal hypertension, abscess in the puncture site, etc..).

• Patients with previous neurological disorders.

• Pregnant women.

• Women who may be pregnant and do not have a negative pregnancy test.

• Breastfeeding women.

• Patients with uncapable to give informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Principe de Asturias	Alcala de Henares	Madrid	Spain	28805
2	Hospital del Henares	Coslada	Madrid	Spain	28822

Sponsors and Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Principe de Asturias
• Spanish Agency of Medicines and Health Products
• Spanish Health Ministry

Investigators

• Principal Investigator: Manuel Ruiz Castro, MD, PhD, Hospital Universitario Principe de Asturias

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fundacion para la Investigacion Biomedica del Hospital Universitario Principe de Asturias
• ClinicalTrials.gov Identifier: NCT02046772
• Other Study ID Numbers: HUPA-EC-01-2012; 2012-000110-11
• First Posted: Jan 28, 2014
• Last Update Posted: Aug 15, 2016
• Last Verified: Aug 1, 2014

• Keywords provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Principe de Asturias: hemorrhoidectomy; analgesia; anaesthetic; bupivacaine; morphine chloride
• Additional relevant MeSH terms: Hemorrhoids; Morphine; Bupivacaine

Study Results

Participant Flow

Arm/Group Title	Bupivacaine + Morphine Chloride	Bupivacaine Standard Dose
Arm/Group Description	People in this arm will receive treatment with morphine chloride (50 mcgr) in addition to a low dose solution of the local intradural anaesthetic bupivacaine (3mg). Bupivacaine low dose: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural. Morphine Chloride: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural.	People in this arm will receive treatment with the standard dose of the local intradural anaesthetic bupivacaine (5mg). Bupivacaine standard dose: Single intradural standard dose of bupivacaine.
Period Title: Overall Study
STARTED	30	33
COMPLETED	30	33
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Bupivacaine + Morphine Chloride	Bupivacaine Standard Dose	Total
Arm/Group Description	People in this arm will receive treatment with morphine chloride (50 mcgr) in addition to a low dose solution of the local intradural anaesthetic bupivacaine (3mg). Bupivacaine low dose: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural. Morphine Chloride: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural.	People in this arm will receive treatment with the standard dose of the local intradural anaesthetic bupivacaine (5mg). Bupivacaine standard dose: Single intradural standard dose of bupivacaine.	Total of all reporting groups
Overall Participants	30	33	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.8 (10.5)	51.3 (10.8)	48.7 (10.9)
Sex: Female, Male (Count of Participants)
Female	13 43.3%	13 39.4%	26 41.3%
Male	17 56.7%	20 60.6%	37 58.7%
Region of Enrollment (participants) [Number]
Spain	30 100%	33 100%	63 100%
BMI (Kg*m^-2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg*m^-2]	25.1 (3.3)	27.2 (4)	26.2 (3.9)
ASA (participants) [Number]
ASA I	7 23.3%	8 24.2%	15 23.8%
ASA II	22 73.3%	25 75.8%	47 74.6%
ASA III	1 3.3%	0 0%	1 1.6%
Number of haemorrhoidal packs removed (participants) [Number]
1 haemorrhoidal pack	8 26.7%	12 36.4%	20 31.7%
2 haemorrhoidal packs	12 40%	13 39.4%	25 39.7%
3 haemorrhoidal packs	8 26.7%	8 24.2%	16 25.4%
Unavailable	2 6.7%	0 0%	2 3.2%
Need of pre-surgery sedation (participants) [Number]
Yes	23 76.7%	23 69.7%	46 73%
No	7 23.3%	10 30.3%	17 27%
Duration of surgery (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	28 (11.1)	20.4 (9.2)	24 (10.8)

Outcome Measures

1. Primary Outcome

Title	Measurement of Time to Start the Anaesthetic Effect
Description	To compare whether the addition of morphine chloride to a low dose intradural solution of the local anaesthetic bupivacaine is as effective as an administration of a single dose of bupivacaine.
Time Frame	First 20 minutes between administration and beginning of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine + Morphine Chloride	Bupivacaine Standard Dose
Arm/Group Description	People in this arm will receive treatment with morphine chloride (50 mcgr) in addition to a low dose solution of the local intradural anaesthetic bupivacaine (3mg). Bupivacaine low dose: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural. Morphine Chloride: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural.	People in this arm will receive treatment with the standard dose of the local intradural anaesthetic bupivacaine (5mg). Bupivacaine standard dose: Single intradural standard dose of bupivacaine.
Measure Participants	30	33
Time to sensitive blocking	2.1 (1.8)	1.6 (1.5)
Time to motor blocking	7.7 (5.9)	4.7 (3.3)

2. Primary Outcome

Title	Measurement of the Analgesic Effect After Surgery by VAS From 0 to 10, Where 0 is no Pain and 10 is the Worst Pain Imaginable.
Description	To compare whether the addition of morphine chloride to a low dose solution of bupivacaine and improves the analgesic treatment than a single administration of bupivacaine.
Time Frame	Up to 72 hours from the end of the surgery in the hospital stay and during the next 7 days at home, after discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine + Morphine Chloride	Bupivacaine Standard Dose
Arm/Group Description	People in this arm will receive treatment with morphine chloride (50 mcgr) in addition to a low dose solution of the local intradural anaesthetic bupivacaine (3mg). Bupivacaine low dose: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural. Morphine Chloride: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural.	People in this arm will receive treatment with the standard dose of the local intradural anaesthetic bupivacaine (5mg). Bupivacaine standard dose: Single intradural standard dose of bupivacaine.
Measure Participants	30	33
VAS at the enter in the reanimation unit	0.03 (0.1)	0.15 (0.7)
VAS after 10 minutes in reanimation unit	0 (0)	0.3 (1)
VAS after 30 minutes in reanimation unit	0.06 (0.3)	0.72 (1.5)
VAS day 1 after surgery	1.5 (1.2)	3.3 (2.2)
VAS day 2 after surgery	3.8 (2.8)	4 (2.5)
VAS day 3 after surgery	3.7 (2.7)	4.5 (2.3)
VAS day 4 after surgery	3.6 (2.6)	4.4 (2.3)
VAS day 5 after surgery	3.6 (2.3)	4 (2.2)
VAS day 6 after surgery	3.2 (2.6)	3.5 (2.3)
VAS day 7 after surgery	2.5 (2.3)	3 (2.2)

3. Secondary Outcome

Title	Greater and Earlier Mobilization Measured by Bromage Scale.
Description	To assess whether the administration of morphine chloride in addition to a low dose solution of local intradural anaesthetic (bupivacaine) improves the mobilization of the patients after surgery more than the single intradural administration of bupivacaine. Total Score in the Bromage Scale goes from 1 to 5, where: 1: complete motor blocking - 2: capable to move the feet - 3: moves the feet and bends the knee - 4: raise the leg straight more or less than 30 degrees but no against resistance - 5: raise the leg straight more than 30 degrees against resistance (no motor blocking)
Time Frame	During the first 24 hours after surgery and at the entry and exit of the resuscitation unit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine + Morphine Chloride	Bupivacaine Standard Dose
Arm/Group Description	People in this arm will receive treatment with morphine chloride (50 mcgr) in addition to a low dose solution of the local intradural anaesthetic bupivacaine (3mg). Bupivacaine low dose: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural. Morphine Chloride: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural.	People in this arm will receive treatment with the standard dose of the local intradural anaesthetic bupivacaine (5mg). Bupivacaine standard dose: Single intradural standard dose of bupivacaine.
Measure Participants	30	33
Bromage at the exit of surgery	4 (1.3)	3.7 (1)
Bromage at the enter in the reanimation unit	4.1 (1.1)	3.8 (1)
Bromage at the exit of the reanimation unit	4.7 (0.4)	4.8 (0.3)

4. Secondary Outcome

Title	Number of Adverse Events
Description	To assess if the experimental treatment causes less, equal or more adverse events than the comparator treatment.
Time Frame	Up to 72 hours from the intervention and the hopitalary stay and during the next 7 days after discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine + Morphine Chloride	Bupivacaine Standard Dose
Arm/Group Description	People in this arm will receive treatment with morphine chloride (50 mcgr) in addition to a low dose solution of the local intradural anaesthetic bupivacaine (3mg). Bupivacaine low dose: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural. Morphine Chloride: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural.	People in this arm will receive treatment with the standard dose of the local intradural anaesthetic bupivacaine (5mg). Bupivacaine standard dose: Single intradural standard dose of bupivacaine.
Measure Participants	30	33
Pruritus	2 6.7%	0 0%
Urinary retention	7 23.3%	3 9.1%
Nausea/Vomits	0 0%	1 3%
Fever	1 3.3%	0 0%

5. Secondary Outcome

Title	Time of Hospitalization
Description	To see if the hospitalization time is shortened or not by the experimental treatment.
Time Frame	Up to 72 hours after the intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine + Morphine Chloride	Bupivacaine Standard Dose
Arm/Group Description	People in this arm will receive treatment with morphine chloride (50 mcgr) in addition to a low dose solution of the local intradural anaesthetic bupivacaine (3mg). Bupivacaine low dose: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural. Morphine Chloride: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural.	People in this arm will receive treatment with the standard dose of the local intradural anaesthetic bupivacaine (5mg). Bupivacaine standard dose: Single intradural standard dose of bupivacaine.
Measure Participants	30	33
1 day of hospitalization	26 86.7%	30 90.9%
2 days of hospitalization	3 10%	2 6.1%
3 days of hospitalization	1 3.3%	1 3%

Adverse Events

Arm/Group Title	Bupivacaine + Morphine Chloride		Bupivacaine Standard Dose
Arm/Group Description	People in this arm will receive treatment with morphine chloride (50 mcgr) in addition to a low dose solution of the local intradural anaesthetic bupivacaine (3mg). Bupivacaine low dose: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural. Morphine Chloride: A dose of morphine chloride added to a low dose solution of bupivacaine administered intradural.		People in this arm will receive treatment with the standard dose of the local intradural anaesthetic bupivacaine (5mg). Bupivacaine standard dose: Single intradural standard dose of bupivacaine.
All Cause Mortality
	Bupivacaine + Morphine Chloride		Bupivacaine Standard Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bupivacaine + Morphine Chloride		Bupivacaine Standard Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Bupivacaine + Morphine Chloride		Bupivacaine Standard Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/30 (33.3%)		4/33 (12.1%)
Gastrointestinal disorders
Nausea or Vomits	0/30 (0%)	0	1/33 (3%)	1
General disorders
Fever	1/30 (3.3%)	1	0/33 (0%)	0
Renal and urinary disorders
Urinary retention	7/30 (23.3%)	7	3/33 (9.1%)	3
Skin and subcutaneous tissue disorders
Pruritus	2/30 (6.7%)	2	0/33 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.