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Pain, PostoperativePhase 4NCT03534895

Does the Preoperative Midazolam Dose Affect Postoperative Pain?

A Phase 4 study testing Midazolam Injectable Solution, Normal saline and Spinal anesthesia in people with Pain, Postoperative, run by Universidade do Porto at 2 sites in Portugal.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

To investigate whether midazolam has any effect on postoperative pain in outpatient surgery, the investigators will assess the impact of different midazolam doses on pain scores 24h, 7 days and 3 months after ambulatory surgery. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pain, Postoperative
What is being tested?
Midazolam Injectable Solution, Normal saline and Spinal anesthesia
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
168 participants
Where
2 sitesPortugal
Study dates
May 2019to Aug 2020
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

  • adult patients submitted to open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery in Portuguese ambulatory surgery units

Who cannot join

  • psychiatric disorders
  • alcoholism
  • illiteracy or poor understanding of Portuguese language
  • history of chronic pain under opioids
  • recurrent surgery
  • contraindication for midazolam or deep sedation
  • contraindication for spinal anesthesia

Trial locations and contacts

2 sites in 1 country.

Caroline Dahlem, MD contact

+351968061851

caroline.dahlem@gmail.com

Portugal2 sites

  • Centro Hospitalar Entre Douro e Vouga, EPE

    Santa Maria da Feira

    Caroline Dahlem, MD

  • Centro Hospitalar Vila Nova de Gaia / Espinho, EPE

    Vila Nova de Gaia

    Carmen Oliveira, MD

Other trials in Portugal

About this study

Official title: Does the Preoperative Midazolam Dose Affect Postoperative Pain? - a Multicentric Randomized Controlled Trial in Ambulatory Surgery

To investigate whether midazolam has any effect on postoperative pain in outpatient surgery, the investigators will assess the impact of different midazolam doses on pain scores 24h, 7 days and 3 months after ambulatory surgery.

The investigators hypothesize that patients being administered higher midazolam doses will refer more pain.

Read the detailed description

Systemic midazolam prescribed perioperatively might have impact on pain, with studies suggesting antinociceptive and hyperalgesic effects. Anxiety might be a confounder in this association. In order to investigate the effect of midazolam on postoperative pain, a clinical trial will be conducted in Portuguese ambulatory surgery units. A convenience sample with consecutive design will include patients admitted for open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery under spinal anesthesia. Patients will be randomized into 3 premedication groups, and this randomization will be stratified for each centre and each type of surgery. Postoperative pain will be blindly assessed by telephone interviews at 24h, 7 days, and 3 months.

The investigators will use multiple regression models to explore the interaction of midazolam dose with preoperative anxiety, gender and chronic benzodiazepine use, as they hypothesize there might be a differential effect of midazolam on postoperative pain amongst these subgroups.

Being tested
Midazolam Injectable Solution, Normal saline, Spinal anesthesia, Surgery, Postoperative analgesia
Keywords
midazolam, ambulatory surgery
Medical subject headings
Pain, Postoperative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Midazolam Injectable SolutionDrug

    Also called Dormicum

    intravenous

  • Normal salineOther

    intravenous

  • Spinal anesthesiaProcedure or surgery

    8mg of heavy bupivacaine 0.5% injected in the subarachnoid space, during lateral decubitus

  • SurgeryProcedure or surgery

    Open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery

  • Postoperative analgesiaDrug

    IV acetaminophen 1g + IV ketorolac 30mg

  • Rescue analgesiaDrug

    Tramadol 2mg/Kg IV in 100mL of normal saline, if pain NRS>3.

  • Wound infiltrationDrug

    Wound infiltration with 10mL of ropivacaine 0.75%, in open inguinal hernia repair

  • Analgesia at homeDrug

    Oral acetaminophen 1g 6/6h + ibuprofen 400mg 8/8h (+ rescue analgesia with tramadol 50mg 6/6h)

Study groups in NCT03534895
Study groupRoleWhat they receive
PC1Placebo comparator5mL normal saline intravenous, single-administration, as pre-medication
Receives: Other: Normal saline; Procedure: Spinal anesthesia; Procedure: Surgery; Drug: Postoperative analgesia; Drug: Rescue analgesia; Drug: Wound infiltration; Drug: Analgesia at home
PC2Experimentalmidazolam 0.02mg/Kg in 5mL normal saline, intravenous, single-administration, as pre-medication
Receives: Drug: Midazolam Injectable Solution; Other: Normal saline; Procedure: Spinal anesthesia; Procedure: Surgery; Drug: Postoperative analgesia; Drug: Rescue analgesia; Drug: Wound infiltration; Drug: Analgesia at home
PC3Experimentalmidazolam 0.06mg/Kg in 5mL normal saline, intravenous, single-administration, as pre-medication
Receives: Drug: Midazolam Injectable Solution; Other: Normal saline; Procedure: Spinal anesthesia; Procedure: Surgery; Drug: Postoperative analgesia; Drug: Rescue analgesia; Drug: Wound infiltration; Drug: Analgesia at home

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Postoperative pain

    Assessed by the Brief Pain Inventory severity score (24h recall time): mean of 4 items assessing pain at the moment of the interview, on average, at its least and at its worst during the last 24h

    Measured: Day 1 after surgery

Secondary outcomes (11)

  1. Postoperative pain

    Assessed by the Brief Pain Inventory severity score (24h recall time): mean of 4 items assessing pain at the moment of the interview, on average, at its least and at its worst during the last 24h. Features of neuropathic pain as assessed by DN4 patient-reported symptoms

    Measured: Day 7 after surgery

  2. Postoperative pain

    Assessed by the Brief Pain Inventory severity score (24h recall time): mean of 4 items assessing pain at the moment of the interview, on average, at its least and at its worst during the last 24h. Features of neuropathic pain as assessed by DN4 patient-reported symptoms

    Measured: Month 3 after surgery

  3. Pain interference in daily life

    Assessed by the Brief Pain Inventory interference score (24h recall time): interference of pain in general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life.

    Measured: Day 1 after surgery

  4. Pain interference in daily life

    Assessed by the Brief Pain Inventory interference score (24h recall time): interference of pain in general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life.

    Measured: Day 7 after surgery

  5. Pain interference in daily life

    Assessed by the Brief Pain Inventory interference score (24h recall time): interference of pain in general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life.

    Measured: Month 3 after surgery

  6. Analgesic consumption

    Total analgesic drugs taken in a time period (first day after surgery)

    Measured: Day 1 after surgery

  7. Analgesic consumption

    Total analgesic drugs taken in a time period (first week after surgery)

    Measured: Day 7 after surgery

  8. Patient satisfaction

    NRS 0-10

    Measured: Day 7 after surgery

  9. Patient satisfaction

    NRS 0-10

    Measured: Month 3 after surgery

  10. Adverse events

    Number of patients with adverse events like bleeding, nausea, uncontrolled pain

    Measured: Day 7 after surgery

  11. Global surgery recovery index

    Global surgery recovery index (0-100%)

    Measured: Month 3 after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2018
  2. Study startMay 2019 (estimated)
  3. Primary completionMay 2020 (estimated)
  4. Study completionAug 2020 (estimated)

Resources

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
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
168 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03534895
Sponsor's protocol ID
Midazolam RCT
Status last verified
May 2018
First submitted
22 Apr 2018
Last updated
23 May 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie the results reported in this article might be shared with other researchers after deidentification.

Publications

  • Mantegazza P, Parenti M, Tammiso R, Vita P, Zambotti F, Zonta N. Modification of the antinociceptive effect of morphine by centrally administered diazepam and midazolam. Br J Pharmacol. 1982 Apr;75(4):569-72. doi: 10.1111/j.1476-5381.1982.tb09175.x.

    PubMed 6121598

  • Tatsuo MA, Salgado JV, Yokoro CM, Duarte ID, Francischi JN. Midazolam-induced hyperalgesia in rats: modulation via GABA(A) receptors at supraspinal level. Eur J Pharmacol. 1999 Apr 1;370(1):9-15. doi: 10.1016/s0014-2999(99)00096-5.

    PubMed 10323274

  • Frolich MA, Zhang K, Ness TJ. Effect of sedation on pain perception. Anesthesiology. 2013 Mar;118(3):611-21. doi: 10.1097/ALN.0b013e318281592d.

    PubMed 23314164

  • Kain ZN, Sevarino F, Pincus S, Alexander GM, Wang SM, Ayoub C, Kosarussavadi B. Attenuation of the preoperative stress response with midazolam: effects on postoperative outcomes. Anesthesiology. 2000 Jul;93(1):141-7. doi: 10.1097/00000542-200007000-00024.

    PubMed 10861157

  • Day MA, Rich MA, Thorn BE, Berbaum ML, Mangieri EA. A placebo-controlled trial of midazolam as an adjunct to morphine patient-controlled analgesia after spinal surgery. J Clin Anesth. 2014 Jun;26(4):300-8. doi: 10.1016/j.jclinane.2013.12.011. Epub 2014 Jun 2.

    PubMed 24882605

  • Okulicz-Kozaryn I, Kaminska E, Luczak J, Szczawinska K, Kotlinska-Lemieszek A, Baczyk E, Mikolajczak P. The effects of midazolam and morphine on analgesic and sedative activity of ketamine in rats. J Basic Clin Physiol Pharmacol. 2000;11(2):109-25. doi: 10.1515/jbcpp.2000.11.2.109.

    PubMed 11037766

  • Hasani A, Maloku H, Sallahu F, Gashi V, Ozgen SU. Preemptive analgesia with midazolam and diclofenac for hernia repair pain. Hernia. 2011 Jun;15(3):267-72. doi: 10.1007/s10029-010-0772-y. Epub 2010 Dec 28.

    PubMed 21188440

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Midazolam Injectable Solution, Normal saline and Spinal anesthesia in people with Pain, Postoperative, run by Universidade do Porto at 2 sites in Portugal.

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 7 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: status not confirmed, as of the sponsor's last update on 23 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Portugal. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Caroline Dahlem, MD (+351968061851, caroline.dahlem@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Postoperative pain (time frame: Day 1 after surgery). 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 NCT03534895, which also lists 7 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 23 May 2018.

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