Efficacy and Safety Study of Ketorolac / Pitofenone / Fenpiverinium for the Treatment of Patients With Pain After Surgical Abdominal and Pelvic Operations

NCT ID: NCT05607641

Last Updated: 2022-11-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

424 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-07

Study Completion Date

2022-05-13

Brief Summary

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Neospastil (ketorolac tromethamine / pitofenone hydrochloride / fenpiverinium bromide fixed-dose combination) in a form of solution for injections and film-coated tablets has been studied as a treatment for pain after surgical abdominal and pelvic operations. The aim of the study was to test the hypothesis that Neospastil was non-inferior (phase II) and superior (phase III) than ketorolac tromethamine monotherapy due to the additional relaxing effect of pitofenone and fenpiverinium on the smooth muscles of internal organs. The study also aimed to show that Neospastil is safe and well-tolerated in people who have pain after surgical abdominal and pelvic operations. Study treatment was initiated with parenteral form of study drug (first 24 hours) and then switched to oral formulation. This trial was conducted in accordance with the ethical principles of Good Clinical Practice and International Council for Harmonization (ICH) Harmonized Tripartite Guidelines.

Detailed Description

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Conditions

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Postsurgical Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A prospective, multicenter, randomized, open-label, parallel-group comparative clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ketorolac tromethamine, solution for injection then Neospastil, film-coated tablets

Group Type OTHER

Ketorolac tromethamine, solution for injection then Neospastil, film-coated tablets

Intervention Type DRUG

These medicines were used for patients of Group 1 (phase II) and Group 4 (phase III).

Stage 1 (1st day of study treatment) - Ketorolac tromethamine, solution for injection, 1 ml every 8 hours.

Stage 2 (2nd day of study treatment) - Neospastil, film-coated tablets, 1 tablet every 6 hours.

Stage 3 (3rd-5th days of study treatment) - Neospastil, film-coated tablets, 1 tablet on demand with an interval of at least 6 hours, not more than 4 tablets per day.

Ketorolac tromethamine, solution for injection then Ketorolac tromethamine, coated tablets

Group Type ACTIVE_COMPARATOR

Ketorolac tromethamine, solution for injection then Ketorolac tromethamine, coated tablets

Intervention Type DRUG

These medicines were used for patients of Group 2 (phase II) and Group 5 (phase III).

Stage 1 (1st day of study treatment) - Ketorolac tromethamine, solution for injection, 1 ml every 8 hours.

Stage 2 (2nd day of study treatment) - Ketorolac tromethamine, coated tablets, 1 tablet every 6 hours.

Stage 3 (3rd-5th days of study treatment) - Ketorolac tromethamine, coated tablets, 1 tablet on demand with an interval of at least 6 hours, not more than 4 tablets per day.

Neospastil, solution for injection then Neospastil, film-coated tablets

Group Type EXPERIMENTAL

Neospastil, solution for injection then Neospastil, film-coated tablets

Intervention Type DRUG

These medicines were used for patients of Group 3 (phase II) and Group 6 (phase III).

Stage 1 (1st day of study treatment) - Neospastil, solution for injection, 2 ml every 8 hours.

Stage 2 (2nd day of study treatment) - Neospastil, film-coated tablets, 1 tablet every 6 hours.

Stage 3 (3rd-5th days of study treatment) - Neospastil, film-coated tablets, on demand 1 tablet with an interval of at least 6 hours, not more than 4 tablets per day.

Interventions

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Ketorolac tromethamine, solution for injection then Neospastil, film-coated tablets

These medicines were used for patients of Group 1 (phase II) and Group 4 (phase III).

Stage 1 (1st day of study treatment) - Ketorolac tromethamine, solution for injection, 1 ml every 8 hours.

Stage 2 (2nd day of study treatment) - Neospastil, film-coated tablets, 1 tablet every 6 hours.

Stage 3 (3rd-5th days of study treatment) - Neospastil, film-coated tablets, 1 tablet on demand with an interval of at least 6 hours, not more than 4 tablets per day.

Intervention Type DRUG

Ketorolac tromethamine, solution for injection then Ketorolac tromethamine, coated tablets

These medicines were used for patients of Group 2 (phase II) and Group 5 (phase III).

Stage 1 (1st day of study treatment) - Ketorolac tromethamine, solution for injection, 1 ml every 8 hours.

Stage 2 (2nd day of study treatment) - Ketorolac tromethamine, coated tablets, 1 tablet every 6 hours.

Stage 3 (3rd-5th days of study treatment) - Ketorolac tromethamine, coated tablets, 1 tablet on demand with an interval of at least 6 hours, not more than 4 tablets per day.

Intervention Type DRUG

Neospastil, solution for injection then Neospastil, film-coated tablets

These medicines were used for patients of Group 3 (phase II) and Group 6 (phase III).

Stage 1 (1st day of study treatment) - Neospastil, solution for injection, 2 ml every 8 hours.

Stage 2 (2nd day of study treatment) - Neospastil, film-coated tablets, 1 tablet every 6 hours.

Stage 3 (3rd-5th days of study treatment) - Neospastil, film-coated tablets, on demand 1 tablet with an interval of at least 6 hours, not more than 4 tablets per day.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age of 18-64 years inclusive and body weight of ≥ 50 kg.
2. The estimated need to use the first dose of the IMP no later than 8 hours after the completion of minimally invasive surgical abdominal and pelvic operations.
3. Immediately before randomization, there is a moderate to severe pain associated with minimally invasive surgical abdominal and pelvic operation (the overall assessment of pain at rest is 4-8 points inclusively in 11-point NRS).
4. At the time of minimally invasive surgery, the patient's condition corresponded to the class I-III of general anesthesia risk according to the classification of the American Society of Anesthesiologists (ASA).
5. The patient is able to adequately assess his/her condition and fill in yourself the patient's diary.
6. The patient agrees to participate in the clinical trial and fulfill all the requirements of the trial and has signed the informed consent form.
7. According to the investigator, IMP is an adequate tactic for postoperative analgesia.

Exclusion Criteria

1. Hypersensitivity or allergic reactions/conditions associated with ketorolac, pitofenone, fenpiverinium, any other components of IMPs, acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
2. The patient has another disease/condition that requires constant use of non-topical analgesics and/or anti-inflammatory agents or, in the opinion of the investigator, disturbs the patient's perception of postoperative pain.
3. The need for postoperative treatment in the intensive care unit for any reason.
4. Active peptic ulcer, recent gastrointestinal bleeding or perforation, history of peptic ulcer or gastrointestinal bleeding.
5. History of bronchial asthma.
6. Severe heart failure (class III-IV according to NYHA).
7. Severe liver failure (including an increase in the activity of alanine aminotransferase and/or aspartate aminotransferase in the blood more than three times the upper limit of normal).
8. Moderate to severe renal failure (blood creatinine concentration \> 160 μmol/l).
9. Suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, including blood coagulation disorders and high risk of bleeding.
10. Dehydration with the risk of kidney failure due to a decrease in the volume of circulating blood.
11. Benign prostatic hyperplasia of the ΙΙ and ΙΙΙ degree.
12. Cardiovascular diseases in which an increase in heart rate may be undesirable (for example, atrial fibrillation, tachycardia \[pulse rate at rest \> 100 bpm\], severe arterial hypertension), as well as an artificial pacemaker.
13. Glaucoma.
14. Signs of intestinal obstruction and/or history of megacolon.
15. Anemia (hemoglobin concentration \< 90 g/l) and/or leukopenia (leukocyte count \< 3.2x109/l) according to the results of preoperative laboratory examination.
16. Diseases or conditions that make it impossible to take drugs orally in accordance with the Clinical Trial Protocol and/or disrupt their absorption in the gastrointestinal tract.
17. The use of drugs prohibited by the Clinical Trial Protocol before the start of study treatment and/or the need to use drugs prohibited by the Clinical Trial Protocol during the investigational treatment.
18. Mental disorder/illness, which, in the opinion of the investigator, may prevent the patient from fulfilling all the requirements of the trial.
19. Pregnancy or lactation.
20. Within 30 days prior to randomization, the use of a drug or medical product in another clinical trial.
21. The patient has already been previously randomized in this trial.

Criteria to start the 2nd stage of treatment, the patient had to meet the criteria for switching to IMP for oral administration:

* pain level of 4-6 points at movements according to the 11-point Numerical Rating Scale (NRS) (7 points were allowed, if pain level at rest did not exceed 6 points according to 11-point NRS);
* no more than 12 hours have passed since the last use of IMP;
* oral analgesic use is an adequate tactic for postoperative analgesia.
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Darnitsa Pharmaceutical Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Regional municipal nonprofitable institution "Chernivtsi regional clinical hospital", urological department

Chernivtsi, , Ukraine

Site Status

Communal enterprise "Dnipropetrovsk Regional Clinical Hospital named after І.І. Mechnikov" Dnipropetrovsk Regional Council", urology department №1

Dnipro, , Ukraine

Site Status

Communal enterprise "Dnipropetrovsk Regional Clinical Hospital named after І.І. Mechnikov" Dnipropetrovsk Regional Council", urology department №2

Dnipro, , Ukraine

Site Status

Communal noncomercial enterprise of the Kharkiv Regional Council "Regional Medical Clinical Center of Urology and Nephrology named after V.I. Shapovala", urology department №5

Kharkiv, , Ukraine

Site Status

Communal noncomercial enterprise "Kyiv City Clinical Hospital #3" Kyiv City Council (Kyiv City State Administration), urological department

Kyiv, , Ukraine

Site Status

Medical Center of the LLC "Harmony of Beauty"

Kyiv, , Ukraine

Site Status

State Institution "Institute of Urology of the National Academy of Medical Sciences of Ukraine", I Urological Department

Kyiv, , Ukraine

Site Status

Communal noncomercial enterprise of the Lviv Regional Council "Lviv Regional Clinical Hospital", department of urology

Lviv, , Ukraine

Site Status

Municipal Non-profit Enterprise "Lviv Clinical Hospital for Emergency Medical Care"

Lviv, , Ukraine

Site Status

Communal noncomercial enterprise "City Clinical Hospital #10" Odesa City Council, urological department #2

Odesa, , Ukraine

Site Status

Medical-diagnostic center" Zakarpattya center of surgical innovations" Astra-med "of limited liability company" Clinic of healthy family "Astramed"

Uzhhorod, , Ukraine

Site Status

Communal noncomercial enterprise" Vinnytsia City Clinical Hospital" Mother and Child Center", department of gynecology with minimally invasive operations

Vinnytsia, , Ukraine

Site Status

Limited Liability Company "Innomed Center of Endosurgery"

Vinnytsia, , Ukraine

Site Status

Communal noncomercial enterprise "City Hospital of Emergency and Ambulance" of Zaporizhia City Council, Department of Surgery with the Center for Gastrointestinal Bleeding

Zaporizhzhya, , Ukraine

Site Status

Countries

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Ukraine

Other Identifiers

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KPF07-T

Identifier Type: -

Identifier Source: org_study_id

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