Ibuprofen vs Dipyrone After C-section in Preeclampsia (DIPROFEN)

Use of Ibuprofen Versus Dipyrone in Preeclampsia Submitted to C-section: Randomized Clinical Trial

The goal of this randomized, triple-masked clinical trial is to compare the effectiveness and safety of the use of ibuprofen versus dipyrone for postoperative analgesia in postpartum women with preeclampsia undergoing cesarean section.

The main question it aims to answer are:

• Postoperative pain is similar;
• The frequency of acute kidney injury is similar.

Researchers will compare one group that will receive dipyrone and the other group that will receive ibuprofen to see if Postoperative pain are different between groups or development of acute kidney injury each group is different.

Study Overview

• Status: Completed
• Conditions: Preeclampsia
• Intervention / Treatment: Drug: medication 1; Drug: medication 2

Detailed Description

Specific objectives

In postpartum women with preeclampsia undergoing cesarean section randomized to receive treatment with ibuprofen versus dipyrone for postoperative analgesia, compare:

primary outcomes

1. Postoperative pain (mild, moderate, severe by visual analogue scale)
2. Development of acute kidney injury (serum creatinine 1.5 to 1.9 times baseline, or increase in serum creatinine by ≥0.3 mg/dL, or decrease in urine output to <0.5 mL/kg/ hour for six to 12 hours).

secondary outcomes

1. Average reduction of visual analogue scale scores;

2 Reduction of mean scores by algometer;

3. Need for rescue analgesic;

4. User satisfaction with the Likert scale;

5. Basic laboratory tests and their evolution: urea, creatine, uric acid, saline, potassium and chlorine, lactic dehydrogenase (DHL), aspartate transferase (AST), alanine transferase (ALT), total and fractions bilirubin and plaque;

6. Evolution of blood pressure in the puerperium;

7. Number of hypertensive peaks;

8. Need for maintenance antihypertensive treatment and number of drugs;

9. Allergic reactions;

10. Gastrointestinal side effects;

11. Time between postoperative and unassisted ambulation;

12. Length of hospital stay;

13. Compound maternal morbidity (eclampsia, acute weight edema, HELLP, difficulty hypertension, intracranial hemorrhage, renal function control and others);

14. Maternal death;

15. Costs related to analgesic medications.

The sample is 74 patients randomized into two groups: one group that will receive dipyrone and the other group that will receive ibuprofen. Randomization for the two groups will be performed according to a list of random numbers drawn up for that purpose by an employee who does not be involved with data collection, to ensure confidentiality in the allocation. From this list, sealed envelopes will be prepared, numbered sequentially, with each number, according to the randomization table, corresponding to the patient's group (dipyrone or ibuprofen).

For statistical analysis of the data, the domain statistical program will be used public Epi-info version 7, or higher versions. Tables will be distributed frequency distribution for categorical variables, calculating the mean and standard deviation of quantitative variables. Then, contingency tables will be used to determine the association of the independent variable (Ibuprofen versus dipyrone) with the dependent variables (Biological characteristics, obstetric features, Maternal clinical parameters at admission and during hospitalization, Maternal laboratory tests at the time of admission). For determination of the strength of association will be calculated as a measure of the risk (RR) and its 95% confidence interval. All p values will be two-tailed and in all stages of the analysis will be considered a level of significance 5%.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Pernambuco
    • Recife, Pernambuco, Brazil, 52020-070
      • IMIP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Puerperal women from 14 years of age diagnosed with preeclampsia with signs of severity Immediate postoperative period;
• Delivery attended at the Maternity from Instituto de Medicina Integral Prof Fernando Figueira.

Exclusion Criteria:

• Acute kidney disease (serum creatinine 1.5 to 1.9 times baseline, or increase in serum creatinine by ≥0.3 mg/dL, or decrease in urine output to <0.5 mL/kg/hour for six to 12 hours)
• Chronic kidney disease;
• Diabetes mellitus;
• Collagenoses;
• Sickle cell anemia;
• Patients who presented bleeding in the pre, trans and immediate postpartum periods;
• Antepartum or puerperal sepsis;
• Known contraindications to the use of NSAIDs and dipyrone;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1; Ibuprofen 400mg 6/6h, oral, maximum 5 days	Drug: medication 1; Ibuprofen pills, identical to the intervention (dipyrone pills), will be administered every 6 hour for a maximum of five days; Other Names: Ibuprofen 400 mg
Experimental: Group 2; Dipyrone 1g 6/6h, oral, maximum 5 days	Drug: medication 2; Dipyrone pills, identical to the intervention (ibuprofen pills), will be administered every 6 hour for a maximum of five days; Other Names: Dipyrone 1g

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain	Postoperative pain (mild, moderate, severe by visual analogue scale)	from 24 after delivery to 48 hours
Development of acute kidney injury	Development of acute kidney injury (serum creatinine 1.5 to 1.9 times baseline, or increase in serum creatinine by ≥0.3 mg/dL, or decrease in urine output to <0.5 mL/kg/ hour for six to 12 hours).	from 24 after delivery to 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean reduction of pain scores by visual analogue scale;	Mean reduction of pain scores by visual analogue scale;	from 24 after delivery to 48 hours
Mean reduction in pain scores assessed by algometer	Mean reduction in pain scores assessed by algometer	from 24 after delivery to 48 hours
need for rescue analgesic therapy;	Quantify the number of times analgesic medication was requested, in addition to what is being offered in the study	from 24 after delivery to 48 hours
User satisfaction level	Likert scale, used in questionnaires, Participants choose from a variety of possible responses to a specific question or statement; responses usually include "strongly agree", "agree", "neutral", "disagree" and "strongly disagree".	from 24 after delivery to 48 hours
urea dosage	Baseline laboratory tests and their evolution, urea measured in mg/dl at admission and up to 48 hours after admission.	from admission in the hospital until 48 hours after delivery
aspartate transferase dosage	Baseline laboratory tests and their evolution, aspartate transferase dosage measured in mg/dl at admission and up to 48 hours after admission.	from admission in the hospital until 48 hours after delivery
potassium dosage	Baseline laboratory tests and their evolution, potassium dosage measured in mg/dl at admission and up to 48 hours after admission.	from admission in the hospital until 48 hours after delivery
chlorine dosage	Baseline laboratory tests and their evolution,chlorine dosage measured in mg/dl at admission and up to 48 hours after admission.	from admission in the hospital until 48 hours after delivery
alanine transferase dosage	Baseline laboratory tests and their evolution, alanine transferase dosage measured in mg/dl at admission and up to 48 hours after admission.	from admission in the hospital until 48 hours after delivery
lactic dehydrogenase dosage	Baseline laboratory tests and their evolution, lactic dehydrogenase dosage measured in mg/dl at admission and up to 48 hours after admission.	from admission in the hospital until 48 hours after delivery
sodium dosage	Baseline laboratory tests and their evolution, sodium dosage measured in mg/dl at admission and up to 48 hours after admission.	from admission in the hospital until 48 hours after delivery
creatinine dosage	Baseline laboratory tests and their evolution, creatinine dosage measured in mg/dl at admission and up to 48 hours after admission.	from admission in the hospital until 48 hours after delivery
c	Baseline laboratory tests and their evolution, creatinine dosage measured in mm³ at admission and up to 48 hours after admission.	from admission in the hospital until 48 hours after delivery
total and fractions bilirubin dosage	Baseline laboratory tests and their evolution: urea, creatinine, uric acid, sodium, potassium and chlorine, lactic dehydrogenase (DHL), aspartate transferase (AST), alanine transferase (ALT), total and fractions bilirubin and platelets;	from admission in the hospital until 48 hours after delivery
uric acid dosage	Baseline laboratory test and the evolution. urea, creatinine, uric acid, sodium, potassium and chlorine, lactic dehydrogenase (DHL), aspartate transferase (AST), alanine transferase (ALT), total and fractions bilirubin and platelets;	from admission in the hospital until 48 hours after delivery
Evolution of blood pressure in the puerperium	Evolution of blood pressure in the puerperium	from 24 after delivery to 48 hours
Number of hypertensive peaks	Number of hypertensive peaks (systolic blood pressure of 180mmHg and/or diastolic blood pressure of 120mmHg);	from 24 after delivery until discharge of the hospital
need for maintenance antihypertensive treatment	Identify the presence or absence of maintenance antihypertensive drugs	from 24 after delivery until discharge of the hospital
number of antihypertensive drugs;	quantify how many antihypertensive medications are being used	from 24 after delivery until discharge of the hospital
Allergic reactions	Questionnaire with options for allergic manifestations: urticaria, angioedema, eczema, asthma.	from 24 after delivery to 48 hours
Gastrointestinal side effects	Questionnaire with options for acute gastrointestinal effects: abdominal pain, dyspepsia and diarrhea	from 24 after delivery to 48 hours
Time between postoperative and unassisted ambulation	Time between postoperative and unassisted ambulation	from 24 after delivery to 48 hours
Length of hospital stay	Length of hospital stay	From hospital admission to hospital discharge date or up to eight days after surgery whichever comes first.
Compound maternal morbidity	Compound maternal morbidity (eclampsia, acute pulmonary edema, HELLP syndrome, difficult-to-control hypertension, intracranial hemorrhage, renal failure and others);	from 24 after delivery until discharge date or up to eight days after surgery whichever comes first.
Maternal death	Space reserved in the questionnaire to be described according to the death certificate the primary cause of maternal death.	from 24 after delivery until discharge date or up to eight days after surgery whichever comes first.
Costs related to analgesic medications	Accounting for the cost related to each dose doses of anesthetic medications that were used in addition to the therapeutic regimens of the experiment were used	from 24 after delivery until discharge date or up to eight days after surgery whichever comes first.

Collaborators and Investigators

• Sponsor: Instituto Materno Infantil Prof. Fernando Figueira

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2022
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: acute kidney injury; cesarean section; analgesia; Preeclampsia; NSAIDs; postpartum period
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pre-Eclampsia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Ibuprofen; Dipyrone
• Other Study ID Numbers: DIPROFEN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No