Septic ShockPhase 4NCT06076980
Heamodynamic Effects of Paracetamol in Septic Shock Patients
A Phase 4 study testing Paracetamol and Normal saline in people with Septic Shock and Sepsis, run by Ayah Mohammed Khalil at 1 site in Egypt.
Trial summary
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is defined as sepsis that has circulatory, cellular, and metabolic abnormalities that are associated with a greater risk of mortality than sepsis alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Sepsis
- What is being tested?
- Paracetamol and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Nov 2020to 24 Jan 2023
- 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
- Age adult ≥ 18 years old.
- The patient fulfills the criteria of septic shock definition:
- Sepsis needs vasopressor therapy.
- Serum lactate level greater than 2 mmol/l (SSC 2016).
- Patient with contractility greater than 40%
Who cannot join
- paracetamol hypersensitivity or allergy.
- Acute liver injury or failure
- Childs-Pugh C liver disease
- Heat stroke.
- Malignant hyperthermia.
- Neuroleptic Malignant Syndrome.
Show all 10Show fewer
- Continous renal replacement therapy.
- Ventricular assist device.
- Around-the-clock scheduled of acetaminophen-containing medications administration or non-steroidal anti-inflammatory drugs.
- Pregnancy/lactation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Haemodynamic Effects of Paracetamol (Acetaminophen) as Extended Intravenous Infusion Versus Intravenous Bolus in Septic Shock Patients
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is defined as sepsis that has circulatory, cellular, and metabolic abnormalities that are associated with a greater risk of mortality than sepsis alone. Clinically, this includes patients who fulfill the criteria for sepsis who, despite adequate fluid resuscitation, require vasopressors to maintain a mean arterial pressure ≥65 mmHg and have a lactate >2 mmol/L (>18 mg/dL). Feve is a common sign of infection in septic shock critically ill patients. Many critically ill patients experience pain. Paracetamol is considered safe and currently one of the most common antipyretics and used as part of multimodal analgesia for acute pain in the intensive care unit. According to the company's product information leaflet, the rate of hypotension complicating intravenous paracetamol treatment ranges from 0.01 to 0.1%. However, recent studies reported a much higher incidence and may be harmful in critically ill adults. The hemodynamic effects of intravenous (IV) paracetamol are unknown in septic shock patients, that the most vulnerable population and hemodynamically unstable.
The aim of this study is to assess the incidence of hypotension of the extended intravenous paracetamol (acetaminophen) infusion over three hours in comparing with intravenous paracetamol bolus over 15 minutes in hemodynamically unstable patients (septic shock).
Read the detailed description
Sepsis, inflammatory response to infection, contributes directly or indirectly to mortality in the majority of critically ill patients. An elevated cardiac index and a decreased systemic vascular resistance leading to hypotension and hypoperfusion of vital organs characterize the early stage of septic shock. The hypotensive state is often not amenable to fluid resuscitation alone and requires institution of vasoactive agents to counter the profound fall in systemic vascular resistance, which is an integral feature of septic shock .
Acetaminophen is the antipyretic and analgesic that is most often given to hospitalized patients, including those in critical care units. The mechanism of action of acetaminophen remains incompletely understood, but the antipyretic response appears to be due to blocking cyclooxygenase-II and inhibiting prostaglandin-II synthesis in the central nervous system.
Intravenous (IV) acetaminophen has gained popularity for inpatient management of acute pain for its practical and clinical advantages. IV administration is associated with more predictable pharmacokinetic performance compared with rectal (30%-40% bioavailability) and oral dosage forms of acetaminophen (60%-70% bioavailability).
Predictable kinetics as well as ease of IV administration has made it an especially attractive option in the critically ill patients who have altered gut absorption secondary to numerous pathophysiological and therapeutic influences .
IV acetaminophen has shown promise in improving patient satisfaction, managing fever, and decreasing postoperative opioid requirements. These features have made it one of the most widely ordered medications within critical care and surgical services.
Product information for IV acetaminophen lists mild effects such as nausea or vomiting among the most common adverse events (incidence ≥ 5%), with the estimated incidence of more serious adverse effects such as hypotension being <1%. However, there have been an increasing number of randomized controlled trials which indicated that the incidence of IV acetaminophen-induced hypotension may be higher than previously reported by manufacturers. These publications have prompted investigators to look more closely at the possible untoward effects of IV acetaminophen across a variety of populations. . None of these studies examined whether the extended infusion of IV paracetamol can minimize the degree of hypotension in critically heamodynamic unstable patients.
- Conditions
- Septic Shock, Sepsis
- Being tested
- Paracetamol, Normal saline
- Keywords
- acetaminophen, paracetamol, septic shock, hemodynamic effects, blood pressure, icu
- Medical subject headings
- Shock, Septic, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParacetamolDrug
Also called acetaminophen
compare the hemodynamic parameters of paracetamol as bolus versus extended infusion
Normal salineDrug
as placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo group | Placebo comparator | placebo group (100 ml normal saline over 15 minutes) Receives: Drug: Normal saline |
| bolus group | Experimental | bolus group (1000mg/100 ml paracetamol over 15 minutes) Receives: Drug: Paracetamol |
| Extended infusion group | Experimental | Extended infusion (1000mg/100 ml paracetamol over 3 hours) Receives: Drug: Paracetamol |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of hypotension .
defined as a decrease in SBP ≥ 20٪ from baseline, by extended infusion of intravenous paracetamol
Measured: pre intervention and six hours after the intervantion
Secondary outcomes (7)
The changes in hemodynamic parameters
Changes in mean arterial pressure(mmHg), diastolic blood pressure (mmHg)
Measured: pre intervention and six hours after the intervantion
The changes in hemodynamic parameters
Changes in cardiac output ( L/min)
Measured: pre intervention and six hours after the intervantion
The changes in hemodynamic parameters
Changes in heart rate (bpm)
Measured: pre intervention and six hours after the intervantion
The changes in hemodynamic parameters
Changes in central venous pressure (mmHg)
Measured: pre intervention and six hours after the intervantion
The changes in temperature
Changes in temperature (celsius)
Measured: pre intervention and six hours after the intervantion
The changes in vassopresors and fluid bolus
changes in vassopresors infusion rate (mcg/ min) and fluid bolus
Measured: pre intervention and six hours after the intervantion
The changes in vassopresors and fluid bolus
changes in fluid bolus (ml)
Measured: pre intervention and six hours after the intervantion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2023
- Study start1 Nov 2020
- Primary completion1 Nov 2022
- Study completion24 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ayah Mohammed Khalil
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ayah Mohammed Khalil, Al-Azhar University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06076980
- Sponsor's protocol ID
- paracetamol in septic shock
- Status last verified
- Oct 2023
- First submitted
- 25 Sep 2023
- Last updated
- 12 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Maxwell EN, Johnson B, Cammilleri J, Ferreira JA. Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature. Ann Pharmacother. 2019 Oct;53(10):1033-1041. doi: 10.1177/1060028019849716. Epub 2019 May 3.
PubMed 31046402
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haemodynamic Effects of Paracetamol (Acetaminophen) as Extended Intravenous Infusion Versus Intravenous Bolus in Septic Shock Patients
- ClinicalTrials.gov ID
- NCT06076980
- Acronym / sponsor ID
- paracetamol in septic shock
- Conditions
- Septic Shock, Sepsis
- Keywords
- acetaminophen, paracetamol, septic shock, hemodynamic effects, blood pressure, icu
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Ayah Mohammed KhalilUniversity, hospital or other
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 1 Nov 2022 (actual)
- Study completion
- 24 Jan 2023 (actual)
- First posted
- 11 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is defined as sepsis that has circulatory, cellular, and metabolic abnormalities that are associated with a greater risk of mortality than sepsis alone. Clinically, this includes patients who fulfill the criteria for sepsis who, despite adequate fluid resuscitation, require vasopressors to maintain a mean arterial pressure ≥65 mmHg and have a lactate >2 mmol/L (>18 mg/dL). Feve is a common sign of infection in septic shock critically ill patients. Many critically ill patients experience pain. Paracetamol is considered safe and currently one of the most common antipyretics and used as part of multimodal analgesia for acute pain in the intensive care unit. According to the company's product information leaflet, the rate of hypotension complicating intravenous paracetamol treatment ranges from 0.01 to 0.1%. However, recent studies reported a much higher incidence and may be harmful in critically ill adults. The hemodynamic effects of intravenous (IV) paracetamol are unknown in septic shock patients, that the most vulnerable population and hemodynamically unstable.
The aim of this study is to assess the incidence of hypotension of the extended intravenous paracetamol (acetaminophen) infusion over three hours in comparing with intravenous paracetamol bolus over 15 minutes in hemodynamically unstable patients (septic shock).
Detailed description
Sepsis, inflammatory response to infection, contributes directly or indirectly to mortality in the majority of critically ill patients. An elevated cardiac index and a decreased systemic vascular resistance leading to hypotension and hypoperfusion of vital organs characterize the early stage of septic shock. The hypotensive state is often not amenable to fluid resuscitation alone and requires institution of vasoactive agents to counter the profound fall in systemic vascular resistance, which is an integral feature of septic shock .
Acetaminophen is the antipyretic and analgesic that is most often given to hospitalized patients, including those in critical care units. The mechanism of action of acetaminophen remains incompletely understood, but the antipyretic response appears to be due to blocking cyclooxygenase-II and inhibiting prostaglandin-II synthesis in the central nervous system.
Intravenous (IV) acetaminophen has gained popularity for inpatient management of acute pain for its practical and clinical advantages. IV administration is associated with more predictable pharmacokinetic performance compared with rectal (30%-40% bioavailability) and oral dosage forms of acetaminophen (60%-70% bioavailability).
Predictable kinetics as well as ease of IV administration has made it an especially attractive option in the critically ill patients who have altered gut absorption secondary to numerous pathophysiological and therapeutic influences .
IV acetaminophen has shown promise in improving patient satisfaction, managing fever, and decreasing postoperative opioid requirements. These features have made it one of the most widely ordered medications within critical care and surgical services.
Product information for IV acetaminophen lists mild effects such as nausea or vomiting among the most common adverse events (incidence ≥ 5%), with the estimated incidence of more serious adverse effects such as hypotension being <1%. However, there have been an increasing number of randomized controlled trials which indicated that the incidence of IV acetaminophen-induced hypotension may be higher than previously reported by manufacturers. These publications have prompted investigators to look more closely at the possible untoward effects of IV acetaminophen across a variety of populations. . None of these studies examined whether the extended infusion of IV paracetamol can minimize the degree of hypotension in critically heamodynamic unstable patients.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo group | Placebo comparator | Drug: Normal salineplacebo group (100 ml normal saline over 15 minutes) |
| bolus group | Experimental | Drug: Paracetamolbolus group (1000mg/100 ml paracetamol over 15 minutes) |
| Extended infusion group | Experimental | Drug: ParacetamolExtended infusion (1000mg/100 ml paracetamol over 3 hours) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age adult ≥ 18 years old.
- The patient fulfills the criteria of septic shock definition:
- Patient with contractility greater than 40%
Key exclusion criteria (10 listed)
- paracetamol hypersensitivity or allergy.
- Acute liver injury or failure
- Childs-Pugh C liver disease
- Heat stroke.
- Malignant hyperthermia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParacetamolAlso: acetaminophencompare the hemodynamic parameters of paracetamol as bolus versus extended infusion | Drug | Extended infusion group, bolus group |
| Normal salineas placebo | Drug | Placebo group |
Primary outcome
The incidence of hypotension .
Time frame: pre intervention and six hours after the intervantion
defined as a decrease in SBP ≥ 20٪ from baseline, by extended infusion of intravenous paracetamol
7 secondary outcomes
The changes in hemodynamic parameters
Time frame: pre intervention and six hours after the intervantion
The changes in hemodynamic parameters
Time frame: pre intervention and six hours after the intervantion
The changes in hemodynamic parameters
Time frame: pre intervention and six hours after the intervantion
The changes in hemodynamic parameters
Time frame: pre intervention and six hours after the intervantion
The changes in temperature
Time frame: pre intervention and six hours after the intervantion
The changes in vassopresors and fluid bolus
Time frame: pre intervention and six hours after the intervantion
The changes in vassopresors and fluid bolus
Time frame: pre intervention and six hours after the intervantion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
- Background: PubMed 31046402Maxwell EN, Johnson B, Cammilleri J, Ferreira JA. Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature. Ann Pharmacother. 2019 Oct;53(10):1033-1041. doi: 10.1177/1060028019849716. Epub 2019 May 3.
- Individual participant dataSharing planned: No
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Paracetamol and Normal saline in people with Septic Shock and Sepsis, run by Ayah Mohammed Khalil at 1 site in Egypt.
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 5 inclusion and 10 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: finished, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of hypotension . (time frame: pre intervention and six hours after the intervantion). 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 NCT06076980, which also lists 1 linked publication.
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 12 Oct 2023.