Acute Kidney InjuryPhase 2NCT03725267
Melatonin for Renal Protection in Patients Receiving Polymyxin B
A Phase 2 study testing Melatonin Pill in people with Acute Kidney Injury and Melatonin, run by Hospital de Clinicas de Porto Alegre at 2 sites in Brazil.
Trial summary
This study has the objective to evaluate the effect in renal function of 30mg of Melatonin versus placebo in patients ≥18 years old treated with polymyxin B. The development of nephrotoxicity will be evaluated by RIFLE(Risk, Injury, Failure, Loss, End stage renal disease) score and KIM-1 urinary biomarker for the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury, Melatonin, Polymyxin B Adverse Reaction
- What is being tested?
- Melatonin Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 2 sitesBrazil
- Study dates
- 1 Oct 2018to 1 Jul 2021
- Phase
- Phase 2
- 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
- Treatment with polymyxin B ( a second inclusion will be accepted if the end of the previous treatment was more than 30-days before enrollment)
- Agreement with the consent form
Who cannot join
- Suspension of polymyxin B therapy with <48hs
- Death in <48hs
- Dialysis or Glomerular Filtration Rate (GFR) <10 ml/min at the beginning of treatment by the Modification in Diet in Renal Disease (MDRD) formula
- Lactose intolerance
- ICU admission at the beginning of therapy
- Previous regular use of Melatonin
Show all 9Show fewer
- Pregnancy
- Patients deprived from liberty
- Unability to receive oral medication (i.e total parenteral nutrition)
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Pontificia Universidade Católica do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 90619-900
About this study
Official title: Melatonin for Renal Protection in Patients Receiving Polymyxin B:a Randomized Clinical Trial
This study has the objective to evaluate the effect in renal function of 30mg of Melatonin versus placebo in patients ≥18 years old treated with polymyxin B. The development of nephrotoxicity will be evaluated by RIFLE(Risk, Injury, Failure, Loss, End stage renal disease) score and KIM-1 urinary biomarker for the first 14 days of polymyxin B therapy.
Read the detailed description
This will be a randomized, double-blind, placebo controlled, phase 2 superiority trial.
Patients ≥18 years old admitted in two tertiary care hospitals from Porto Alegre-Brazil receiving intravenous polymyxin B (PMB) will be included after agreeing with the informed consent. Exclusion criteria will be use of PMB for less than 48 hours, chronic dialysis or glomerular filtration rate <10ml/min or Intensive Care Unit (ICU) admission at baseline, previous regular use of melatonin, pregnancy, unability to receive oral medications or deprived from liberty individuals. All eligible patients will be consecutively recruited.
Primary outcome will be nephrotoxicity evaluated by RIFLE criteria. Secondary outcomes will be development of Renal Failure (by RIFLE criteria), Kidney Injury Molecule-1 (KIM-1) urinary biomarker evaluated at days 2,4 and 7 after the start of PMB and 30 day mortality. Potential confounding factors will be evaluated, such as: demographic variables, comorbidities, PMB dose, concomitant use of other antimicrobials, though concentration of PMB after the 4th dose of the antibiotic.
Patients will be randomized in a 1:1 ratio by a computer system in blocks of 4 for melatonin 30mg or placebo. Analysis will be stratified by center. Patients, attending physicians and researchers responsible for the intervention and data collection will be blinded.
Univariate analysis of variables that could potentially impact on nephrotoxicity will be done by T-test or Wilcoxon rank-sum and Fisher test according to the variables characteristics. A Cox regression model for time to nephrotoxicity during PMB therapy will be done, censoring patients if death, end of therapy or completion of 14 days of PMB therapy. The main analysis will be for intention- to-treat and a secondary per-protocol analysis will be done for patients that received at least 80% of the planned doses. All tests will be two-sided and P≤0.05 will be considered statistically significant.
A subgroup analysis is planned for patients with baseline glomerular filtration rate ≥60ml/min and ≥60years old.
The calculated sample size for this study is of 100 patients, 50 in each arm. An interim analysis is planned when half of the sample is recruited (25 in each arm). If the number of patients that achieve nephrotoxicity criteria is at least 30% less in one of the arms compared to the other, with a P≤0,01, the study will be interrupted.
- Conditions
- Acute Kidney Injury, Melatonin, Polymyxin B Adverse Reaction
- Being tested
- Melatonin Pill, Placebo oral capsule
- Keywords
- Melatonin, Polymixin B, RIFLE, Nephrotoxicity
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Melatonin PillDrug
Patients will receive 1 pill of melatonin each day during polymyxin B therapy for a maximum of 14 days.
Placebo oral capsuleDrug
Patients will receive 1 pill of placebo each day during polymyxin B therapy for a maximum of 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Experimental | Patients will receive 1 pill each day with 30 mg of Melatonin during polymyxin B treatment for a maximum of 14 days. Receives: Drug: Melatonin Pill |
| Placebo | Placebo comparator | Patients will receive 1 pill each day with Placebo during polymyxin B treatment for a maximum of 14 days. Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Kidney Injury according to RIFLE criteria
Acute Kidney Injury measured by Risk, Injury, Failure, Loss and End Stage Renal Disease (RIFLE) score, which takes in account variations of creatinin levels and glomerular filtration rate compared to baseline values: Risk (R) increase in 1.5 times the creatinine value or decrease >25% glomerular filtration rate; Injury (I) increase in 2.0 times the creatinine value or decrease >50% glomerular filtration rate, Failure (F) increase in 3.0 times the creatinine value or decrease >75% glomerular filtration rate. Due to the study follow-up time we won´t be able to evaluate Loss (L) nor End Stage Renal Disease (E)- which would require at least 4 weeks of renal function monitoring ( we will follow patients only during polymyxin B treatment, up to 14 days).The better outcome would be not fulfilling any RIFLE criteria and the worse outcome would be Failure (F).
Measured: 14 days Renal Failure.
Secondary outcomes (3)
Renal Failure according to RIFLE criteria
Renal failure by RIFLE criteria is considered and increase of 3 times the creatinin values compared to baseline or a decrease of 75% of the glomerular filtration rate.
Measured: 14 days
Kidney Injury Molecule-1 (KIM_1)
Urinary biomarker measured on days 2, 4 and 7 after the beginning of PMB therapy. The rise in the biomarker values (days 4 and 7) compared to baseline (day 2)will be an early measure of kidney injury.
Measured: 7 days
30-day mortality
All cause mortality after 30-days of the beginning of PMB therapy.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2018
- Study start1 Oct 2018
- Primary completion15 Jun 2021
- Study completion1 Jul 2021
Why it stopped: Due to COVID 19 pandemic social isolation measures, we had to stop recruting hospitalized patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double blind, placebo-controlled, 2-arm parallel trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico, Pontificia Universidade Católica do Rio Grande do Sul
- Responsible party
- Sponsor
- Investigators
- Maria Helena P Rigatto, Professor, Principal investigator, Hospital de Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03725267
- Sponsor's protocol ID
- 77374017.1.0000.5327
- Status last verified
- Aug 2021
- First submitted
- 11 Oct 2018
- Last updated
- 27 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We will provide individual participant data if required by direct contact with our PI.
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Melatonin for Renal Protection in Patients Receiving Polymyxin B:a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03725267
- Acronym / sponsor ID
- 77374017.1.0000.5327
- Conditions
- Acute Kidney Injury, Melatonin, Polymyxin B Adverse Reaction
- Keywords
- Melatonin, Polymixin B, RIFLE, Nephrotoxicity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to COVID 19 pandemic social isolation measures, we had to stop recruting hospitalized patients.
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico, Pontificia Universidade Católica do Rio Grande do Sul
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 15 Jun 2021 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 31 Oct 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 has the objective to evaluate the effect in renal function of 30mg of Melatonin versus placebo in patients ≥18 years old treated with polymyxin B. The development of nephrotoxicity will be evaluated by RIFLE(Risk, Injury, Failure, Loss, End stage renal disease) score and KIM-1 urinary biomarker for the first 14 days of polymyxin B therapy.
Detailed description
This will be a randomized, double-blind, placebo controlled, phase 2 superiority trial.
Patients ≥18 years old admitted in two tertiary care hospitals from Porto Alegre-Brazil receiving intravenous polymyxin B (PMB) will be included after agreeing with the informed consent. Exclusion criteria will be use of PMB for less than 48 hours, chronic dialysis or glomerular filtration rate <10ml/min or Intensive Care Unit (ICU) admission at baseline, previous regular use of melatonin, pregnancy, unability to receive oral medications or deprived from liberty individuals. All eligible patients will be consecutively recruited.
Primary outcome will be nephrotoxicity evaluated by RIFLE criteria. Secondary outcomes will be development of Renal Failure (by RIFLE criteria), Kidney Injury Molecule-1 (KIM-1) urinary biomarker evaluated at days 2,4 and 7 after the start of PMB and 30 day mortality. Potential confounding factors will be evaluated, such as: demographic variables, comorbidities, PMB dose, concomitant use of other antimicrobials, though concentration of PMB after the 4th dose of the antibiotic.
Patients will be randomized in a 1:1 ratio by a computer system in blocks of 4 for melatonin 30mg or placebo. Analysis will be stratified by center. Patients, attending physicians and researchers responsible for the intervention and data collection will be blinded.
Univariate analysis of variables that could potentially impact on nephrotoxicity will be done by T-test or Wilcoxon rank-sum and Fisher test according to the variables characteristics. A Cox regression model for time to nephrotoxicity during PMB therapy will be done, censoring patients if death, end of therapy or completion of 14 days of PMB therapy. The main analysis will be for intention- to-treat and a secondary per-protocol analysis will be done for patients that received at least 80% of the planned doses. All tests will be two-sided and P≤0.05 will be considered statistically significant.
A subgroup analysis is planned for patients with baseline glomerular filtration rate ≥60ml/min and ≥60years old.
The calculated sample size for this study is of 100 patients, 50 in each arm. An interim analysis is planned when half of the sample is recruited (25 in each arm). If the number of patients that achieve nephrotoxicity criteria is at least 30% less in one of the arms compared to the other, with a P≤0,01, the study will be interrupted.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized, double blind, placebo-controlled, 2-arm parallel trial
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Experimental | Drug: Melatonin PillPatients will receive 1 pill each day with 30 mg of Melatonin during polymyxin B treatment for a maximum of 14 days. |
| Placebo | Placebo comparator | Drug: Placebo oral capsulePatients will receive 1 pill each day with Placebo during polymyxin B treatment for a maximum of 14 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Treatment with polymyxin B ( a second inclusion will be accepted if the end of the previous treatment was more than 30-days before enrollment)
- Agreement with the consent form
Key exclusion criteria (9 listed)
- Suspension of polymyxin B therapy with <48hs
- Death in <48hs
- Dialysis or Glomerular Filtration Rate (GFR) <10 ml/min at the beginning of treatment by the Modification in Diet in Renal Disease (MDRD) formula
- Lactose intolerance
- ICU admission at the beginning of therapy
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 |
|---|---|---|
| Melatonin PillPatients will receive 1 pill of melatonin each day during polymyxin B therapy for a maximum of 14 days. | Drug | Melatonin |
| Placebo oral capsulePatients will receive 1 pill of placebo each day during polymyxin B therapy for a maximum of 14 days. | Drug | Placebo |
Primary outcome
Acute Kidney Injury according to RIFLE criteria
Time frame: 14 days Renal Failure.
Acute Kidney Injury measured by Risk, Injury, Failure, Loss and End Stage Renal Disease (RIFLE) score, which takes in account variations of creatinin levels and glomerular filtration rate compared to baseline values: Risk (R) increase in 1.5 times the creatinine value or decrease >25% glomerular filtration rate; Injury (I) increase in 2.0 times the creatinine value or decrease >50% glomerular filtration rate, Failure (F) increase in 3.0 times the creatinine value or decrease >75% glomerular filtration rate. Due to the study follow-up time we won´t be able to evaluate Loss (L) nor End Stage Renal Disease (E)- which would require at least 4 weeks of renal function monitoring ( we will follow patients only during polymyxin B treatment, up to 14 days).The better outcome would be not fulfilling any RIFLE criteria and the worse outcome would be Failure (F).
3 secondary outcomes
Renal Failure according to RIFLE criteria
Time frame: 14 days
Kidney Injury Molecule-1 (KIM_1)
Time frame: 7 days
30-day mortality
Time frame: 30 days
Results and safety
The study was stopped early (reason given: Due to COVID 19 pandemic social isolation measures, we had to stop recruting hospitalized patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2021.
- Individual participant dataSharing planned: Undecided. We will provide individual participant data if required by direct contact with our PI.
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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.
Maria Helena P Rigatto, Professor principal investigator
Hospital de Clinicas de Porto Alegre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melatonin Pill in people with Acute Kidney Injury and Melatonin, run by Hospital de Clinicas de Porto Alegre at 2 sites in Brazil.
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 2 inclusion and 9 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: stopped early, as of the sponsor's last update on 27 Aug 2021. 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 Brazil. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Due to COVID 19 pandemic social isolation measures, we had to stop recruting hospitalized patients.). Results are not available in the source record.
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?
Acute Kidney Injury according to RIFLE criteria (time frame: 14 days Renal Failure.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Aug 2021.