Renal Impairment in Hepatorenal SyndromePhase 4NCT03455322
Norepinephrine Infusion Versus Midodrine & Octreotide in Patients With Hepatorenal Syndrome Type 1.
A Phase 4 study testing norepinephrine versus midodrine & octreotide in people with Renal Impairment in Hepatorenal Syndrome, run by National Hepatology & Tropical Medicine Research Institute at 1 site in Egypt.
Trial summary
This study aimed to investigate the efficacy of midodrine plus octreotide versus norepinephrine and to determine the predictive factors of response in patients with HRS-AKI. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Renal Impairment in Hepatorenal Syndrome
- What is being tested?
- norepinephrine versus midodrine & octreotide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Aug 2018to 10 Jul 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients that will be included in the study have cirrhosis as diagnosed by clinical, biochemical, and ultrasound findings, with HRS type 1, the absence of bacterial infections; however, patients with bacterial infections could be included in the study if renal failure persisted after infection resolution by clinical, laboratory indices up to 48 hours.
Who cannot join
- Patients will be excluded if there are advanced cardiovascular diseases due to poor prognosis or any extrahepatic disease that could affect the short-term prognosis, the presence of advanced hepatocellular carcinoma or presence of contraindication to norepinephrine as hypotension due to blood volume deficits except emergency measure, mesenteric or peripheral vascular thrombosis unless there is life-saving procedure, profound hypoxia or hypercarbia.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pros & Cons of Norepinephrine Infusion Versus Midodrine & Octreotide in Patients With Hepatorenal Syndrome Type 1 in Intensive Care Unit.
This study aimed to investigate the efficacy of midodrine plus octreotide versus norepinephrine and to determine the predictive factors of response in patients with HRS-AKI.
Read the detailed description
Both sexes aged 18 years or older having cirrhosis, ascites, and a diagnosis of HRS-AKI based on the 2015 International Club of Ascites (ICA) diagnostic criteria [2] were eligible for participation.
Screening and eligibility criteria were verified upon admission to the ICU. A diagnosis of AKI was established through comparing sCr value at time of ICU admission to that recorded in the patient's file. Patients who meet all other diagnostic criteria of HRS-AKI provided by the previous definition [2] were enrolled in the study. Qualified patients were subjected to baseline assessments after informed consent signature. It included vital sign measurements, presence of comorbidities, height and weight, Child-Pugh score and Sequential Organ Failure Assessment (SOFA) score. Vital signs, Blood urea nitrogen, sCr, serum sodium, serum albumin, total bilirubin, and complete blood count with differential were measured at baseline and at daily basis throughout the study period. Patients were randomized in a 1:1 ratio to receive either continuous infusion of norepinephrine in an initial dose of 0.5mg/h (Maximum 3 mg/h or oral midodrine 5mg three times/day (Maximum 12.5mg three times/day) plus octreotide 100μg/6h as subcutaneous injection (Maximum 200 μg/6h). Duration of treatment was allowed to extend to a maximum of 10 days. Administration of albumin at doses of 20 to 40 gm/day was recommended, as clinically indicated, for all patients in both study arms as per current ICA guidelines.
- Conditions
- Renal Impairment in Hepatorenal Syndrome
- Being tested
- norepinephrine versus midodrine & octreotide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
norepinephrine versus midodrine & octreotideDrug
either intravenous infusion (IVi) norepinephrine in a dose of 0.05-0.3ug/Kg/min. to keep mean arterial pressure ≥ 80-100mmHg \& continued either until HRS reversal or for maximum 10 days or oral midodrine 5mg three times/day \& can be increased every 24h up to 12.5mg three times daily plus octreotide 100ug/ 6h subcutaneous \& if needed increased to 200ug/6h.
| Study group | Role | What they receive |
|---|---|---|
| norepinephrine | Active comparator | norepinephrine continuous intravenous infusion in a dose of 0.05-0.3ug/Kg/min. average7-10 days to keep mean arterial pressure ≥ 80-100mmHg \& continued either until HRS reversal or for maximum 10 days. Receives: Drug: norepinephrine versus midodrine & octreotide |
| midodrine & octreotide | Active comparator | midodrine 5mg three times/day orally \& can be increased every 24h up to 12.5mg three times daily plus octreotide 100ug/ 6h subcutaneous \& if needed increased to 200ug/6hS.C. for 7-10 days Receives: Drug: norepinephrine versus midodrine & octreotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
the proportion of patients achieved full response
defined as return of sCr to a value within 0.3 mg/dl of the baseline value
Measured: within10 days
Secondary outcomes (5)
the proportion of patients achieved partial response
defined as a regression of at least one AKI stage with a fall in the sCr value to ≥0.3 mg/dl above the baseline value
Measured: within 10 days
Incidence of HRS reversal
defined as at least one sCr value of ≤ 1.5 mg/dl while on treatment
Measured: within 10 days
incidence of HRS-AKI relapse
relapse of HRS-AKI after cessation of treatment
Measured: 30 days
overall survival
patients who are survived
Measured: 30 days
adverse events experienced throughout the study period in both treatment groups.
The incidence of hepatic encephalopathy episodes, bacterial infections, gastrointestinal bleeding, myocardial infarction, arrhythmia, circulatory overload and arterial hypertension was assessed at the end of the study. The need for mechanical ventilation and the need for dialysis.
Measured: within 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2018
- Study start15 Aug 2018
- Primary completion20 Apr 2020
- Study completion10 Jul 2020
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 Renal Impairment in Hepatorenal SyndromeStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Hepatology & Tropical Medicine Research Institute
- Sponsor type
- Other government
- Responsible party
- Principal investigator, ICU, National Hepatology & Tropical Medicine Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03455322
- Sponsor's protocol ID
- NHTMRI-2
- Status last verified
- Feb 2021
- First submitted
- 3 Jan 2018
- Last updated
- 23 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
El-Desoki Mahmoud EI, Abdelaziz DH, Abd-Elsalam S, Mansour NO. Norepinephrine is More Effective Than Midodrine/Octreotide in Patients With Hepatorenal Syndrome-Acute Kidney Injury: A Randomized Controlled Trial. Front Pharmacol. 2021 Jul 2;12:675948. doi: 10.3389/fphar.2021.675948. eCollection 2021.
PubMed 34276366
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pros & Cons of Norepinephrine Infusion Versus Midodrine & Octreotide in Patients With Hepatorenal Syndrome Type 1 in Intensive Care Unit.
- ClinicalTrials.gov ID
- NCT03455322
- Acronym / sponsor ID
- NHTMRI-2
- Conditions
- Renal Impairment in Hepatorenal Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Hepatology & Tropical Medicine Research InstituteOther government
- Study start
- 15 Aug 2018 (actual)
- Primary completion
- 20 Apr 2020 (actual)
- Study completion
- 10 Jul 2020 (actual)
- First posted
- 6 Mar 2018 (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.
This study aimed to investigate the efficacy of midodrine plus octreotide versus norepinephrine and to determine the predictive factors of response in patients with HRS-AKI.
Detailed description
Both sexes aged 18 years or older having cirrhosis, ascites, and a diagnosis of HRS-AKI based on the 2015 International Club of Ascites (ICA) diagnostic criteria [2] were eligible for participation.
Screening and eligibility criteria were verified upon admission to the ICU. A diagnosis of AKI was established through comparing sCr value at time of ICU admission to that recorded in the patient's file. Patients who meet all other diagnostic criteria of HRS-AKI provided by the previous definition [2] were enrolled in the study. Qualified patients were subjected to baseline assessments after informed consent signature. It included vital sign measurements, presence of comorbidities, height and weight, Child-Pugh score and Sequential Organ Failure Assessment (SOFA) score. Vital signs, Blood urea nitrogen, sCr, serum sodium, serum albumin, total bilirubin, and complete blood count with differential were measured at baseline and at daily basis throughout the study period. Patients were randomized in a 1:1 ratio to receive either continuous infusion of norepinephrine in an initial dose of 0.5mg/h (Maximum 3 mg/h or oral midodrine 5mg three times/day (Maximum 12.5mg three times/day) plus octreotide 100μg/6h as subcutaneous injection (Maximum 200 μg/6h). Duration of treatment was allowed to extend to a maximum of 10 days. Administration of albumin at doses of 20 to 40 gm/day was recommended, as clinically indicated, for all patients in both study arms as per current ICA guidelines.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| norepinephrine | Active comparator | Drug: norepinephrine versus midodrine & octreotidenorepinephrine continuous intravenous infusion in a dose of 0.05-0.3ug/Kg/min. average7-10 days to keep mean arterial pressure ≥ 80-100mmHg \& continued either until HRS reversal or for maximum 10 days. |
| midodrine & octreotide | Active comparator | Drug: norepinephrine versus midodrine & octreotidemidodrine 5mg three times/day orally \& can be increased every 24h up to 12.5mg three times daily plus octreotide 100ug/ 6h subcutaneous \& if needed increased to 200ug/6hS.C. for 7-10 days |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients that will be included in the study have cirrhosis as diagnosed by clinical, biochemical, and ultrasound findings, with HRS type 1, the absence of bacterial infections; however, patients with bacterial infections could be included in the study if renal failure persisted after infection resolution by clinical, laboratory indices up to 48 hours.
Key exclusion criteria (1 listed)
- Patients will be excluded if there are advanced cardiovascular diseases due to poor prognosis or any extrahepatic disease that could affect the short-term prognosis, the presence of advanced hepatocellular carcinoma or presence of contraindication to norepinephrine as hypotension due to blood volume deficits except emergency measure, mesenteric or peripheral vascular thrombosis unless there is life-saving procedure, profound hypoxia or hypercarbia.
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 |
|---|---|---|
| norepinephrine versus midodrine & octreotideeither intravenous infusion (IVi) norepinephrine in a dose of 0.05-0.3ug/Kg/min. to keep mean arterial pressure ≥ 80-100mmHg \& continued either until HRS reversal or for maximum 10 days or oral midodrine 5mg three times/day \& can be increased every 24h up to 12.5mg three times daily plus octreotide 100ug/ 6h subcutaneous \& if needed increased to 200ug/6h. | Drug | midodrine & octreotide, norepinephrine |
Primary outcome
the proportion of patients achieved full response
Time frame: within10 days
defined as return of sCr to a value within 0.3 mg/dl of the baseline value
5 secondary outcomes
the proportion of patients achieved partial response
Time frame: within 10 days
Incidence of HRS reversal
Time frame: within 10 days
incidence of HRS-AKI relapse
Time frame: 30 days
overall survival
Time frame: 30 days
adverse events experienced throughout the study period in both treatment groups.
Time frame: within 10 days
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 23 Feb 2021.
- Derived from this study: PubMed 34276366El-Desoki Mahmoud EI, Abdelaziz DH, Abd-Elsalam S, Mansour NO. Norepinephrine is More Effective Than Midodrine/Octreotide in Patients With Hepatorenal Syndrome-Acute Kidney Injury: A Randomized Controlled Trial. Front Pharmacol. 2021 Jul 2;12:675948. doi: 10.3389/fphar.2021.675948. eCollection 2021.
- Individual participant dataSharing planned: Yes
Related trials for Renal Impairment in Hepatorenal Syndrome
Active, not recruitingPhase 2
Endothelin Receptor Antagonism With Ambrisentan to Treat Hepatorenal Syndrome
Hepatorenal Syndrome, Liver Cirrhosis
Recruiting
Initial Resuscitation for Acute Kidney Injury in Cirrhosis
Cirrhosis, Liver, Acute Kidney Injury
Not yet recruiting
Renal Histopathology and Transcriptomic Analysis in Hepatorenal Syndrome During Liver Transplantation
Hepatorenal Syndrome, Liver Regeneration, AKI - Acute Kidney Injury
Recruiting
HRS-AKI Treatment With TIPS in Patients With Cirrhosis
Cirrhosis, Liver, Hepatorenal Syndrome
RecruitingObservational study
Non-invasive Evaluation of the Predictive Value of CEUS and SWE in ACLF, Renal Failure and Hepatorenal Syndrome
Kidney Failure, Acute
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 norepinephrine versus midodrine & octreotide in people with Renal Impairment in Hepatorenal Syndrome, run by National Hepatology & Tropical Medicine Research Institute 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 1 inclusion and 1 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 23 Feb 2021. 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. 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 proportion of patients achieved full response (time frame: within10 days). 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 NCT03455322, 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 23 Feb 2021.