Acute Kidney InjuryPhase 3NAKEDNCT02272725
Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances
A Phase 3 study testing Ibuprofen in people with Acute Kidney Injury and Exercise-associated Hyponatremia, run by Stanford University at 1 site in United States.
Trial summary
The specific aim of this study is to evaluate the safety of non-steroidal anti-inflammatory drugs (NSAIDs) and their impact on renal function and/or contribution to exercise-associated hyponatremia (EAH) during an ultramarathon foot race. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Kidney Injury, Exercise-associated Hyponatremia, Perceived Exertion
- What is being tested?
- Ibuprofen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to Jan 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Any participant in a RacingThePlanet sanctioned event who understands the consent form in English.
Who cannot join
- Allergic to any form of non-steroidal anti-inflammatory
- Taken a NSAID or steroid in prior 12 hours
- 1 kidney
- Known to be pregnant or suspected to be pregnant
Trial locations and contacts
1 site in 1 country.
About this study
The specific aim of this study is to evaluate the safety of non-steroidal anti-inflammatory drugs (NSAIDs) and their impact on renal function and/or contribution to exercise-associated hyponatremia (EAH) during an ultramarathon foot race. There is currently much debate over whether NSAID ingestion during endurance events contributes to acute kidney injury. Endurance events often ignite a "perfect storm" of physiologic insults- heat stress, dehydration, and myopathy- which can all negatively impact kidney function. There is a concern that NSAIDs may further potentiate these negative effects as well as contribute to EAH through its anti-diuretic affect. To date, no powered, prospective study has ever examined the effects of NSAIDs on either of these two biochemical outcomes
Ultramarathon endurance events, defined as any race longer than a marathon (26.2 miles), are increasing in popularity, with a 10% increase in annual participants, and more than 69,000 finishers worldwide in 2013. Considerable literature has documented alterations in serum biochemical profiles of these endurance athletes, with consistent evidence of elevated serum creatinine (Cr) levels in healthy race finishers as well as those seeking medical care. While acute renal failure in ultramarathon runners is a rare occurrence, acute kidney injury is common, ranging from 34% in a single-stage ultramarathon to 55-80% in multi-stage ultramarathons. The evidence is equivocal regarding NSAID ingestion and AKI. One study showed that runners who ingested NSAIDs prior to marathons had greater post-race creatinine levels than matched controls as well as higher rates of hospitalization and acute renal failure. However, this contrasts with several other studies that showed a marked lack of difference in creatinine levels or development of acute kidney injury between NSAID users and non-users during ultramarathons. The only randomized trial to date on this subject found no difference in serum creatinine levels between the NSAID and placebo groups at ultramarathon race end, however conclusions were limited by a small unpowered sample size.
Exercise associated hyponatremia (EAH), defined as a serum sodium concentration below 135mEq/L, is recognized as a relatively common issue in endurance running events. The incidence of EAH varies depending upon the distance of the race, with reported values of 3-28% for marathons, 23 - 38% for triathlons and 4-51% in single-stage ultramarathons. EAH is likely under-diagnosed as athletes are often asymptomatic. While EAH most often manifests as non-specific symptoms such as nausea, vomiting, dizziness, and fatigue, it can be a potentially fatal disease that can progress to encephalopathy, seizures, pulmonary edema, and death. There have been no large prospective studies examining the relationship between EAH and NSAID ingestion.
Read the detailed description
This study will be conducted during the fifth stage of a 6-stage ultramarathon foot race that covers a total of 250 kilometers. Data will be collected during four separate events over the course of the coming year. All races are run by the RacingThePlanet™ 4-desert race series with locations including: Jordan, Ecuador, China, and Chile. The evening after stage 4, participants will be reminded to check in at the medical tent prior to stage 5 start, and at that time the participants will be weighed and given their study drug packet (ibuprofen or visually identical placebo). Approximately 80% of the finishers complete the 80-kilometer Stage 5 in less than 19 hours, so the majority of participants will ingest 1600mg of ibuprofen (400mg q 4 hours x 4 doses). The optimal adult dosing for analgesia is 400mg every 4 hours, with a maximum daily dose of 3200mg ((1999). Product information: Motrin™, ibuprofen. Kalamazoo, MI, Pharmacia \& Upjohn Company.)
Immediately after crossing the finish line of Stage 5, participants will be reweighed, then seated in the study tent where a fingertip blood sample will be obtained via lancet and capillary collection tube (Mock, Morrison, \& Yatscoff, 1995) then analyzed for Na, Cr and BUN (utilizing a Chem-8 cartridge) onsite immediately after collection using an iSTAT® point-of- care analyzer (Abbott; East Windsor, NJ). Any participant who did not complete any stage prior to stage 5 will be removed from the competition and the study. Both the point-of-care device and the digital scale will be calibrated for prior to taking measurements. At this point, the study is over and there is no further participant responsibilities.
- Being tested
- Ibuprofen, Placebo
- Keywords
- ultramarathon, ibuprofen, acute kidney injury, exercise-associated hyponatremia, exertion
- 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.
IbuprofenDrug
Also called motrin
Ibuprofen
PlaceboDrug
Also called sugar pill
Tasteless and inert visually identical (to ibuprofen) pills
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | tasteless and inert tablets Receives: Drug: Placebo |
| Ibuprofen | Active comparator | Each tablet containing 400mg of ibuprofen Receives: Drug: Ibuprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Kidney Injury
The participants experiencing acute kidney injury (diagnosed by an increase in creatinine of greater or equal to 1.5x that of estimated baseline creatinine from age and weight) will be from measured point-of-care blood test of the finish line immediately following the completion of a 50 mile ultramarathon. This outcome measure is a biochemical reading, that may not necessarily be a clinical adverse event.
Measured: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours
Secondary outcomes (2)
Perceived Exertion
A Borg score of perceived exertion will be measured at the finish line immediately following completion of a 50 mile ultramarathon to measure what affect ibuprofen had on perceived exertion as analgesia may have made the endurance event perceived as less exertional. Scores range from 7 - 20, with higher scores indicative of greater amount of exertion.
Measured: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours
Exercise-Associated Hyponatremia
The count of participants experiencing exercise-associated hyponatremia (defined as < 135 mEq) will be estimated from measured point-of-care blood test at the finish line immediately following completion of a 50 mile ultramarathon. This outcome measure is a biochemical reading, that may not necessarily be a clinical adverse event.
Measured: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2014 (estimated)
- Study startMar 2015
- Primary completionMar 2016
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Grant S Lipman, Stanford University
- Investigators
- Grant S Lipman, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02272725
- Sponsor's protocol ID
- 31907
- Acronym
- NAKED
- Status last verified
- Nov 2018
- First submitted
- 9 Oct 2014
- Last updated
- 12 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lipman GS, Shea K, Christensen M, Phillips C, Burns P, Higbee R, Koskenoja V, Eifling K, Krabak BJ. Ibuprofen versus placebo effect on acute kidney injury in ultramarathons: a randomised controlled trial. Emerg Med J. 2017 Oct;34(10):637-642. doi: 10.1136/emermed-2016-206353. Epub 2017 Jul 5.
PubMed 28679502
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances
- ClinicalTrials.gov ID
- NCT02272725
- Acronym / sponsor ID
- NAKED / 31907
- Keywords
- ultramarathon, ibuprofen, acute kidney injury, exercise-associated hyponatremia, exertion
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Mar 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 23 Oct 2014 (estimated)
- Results
- Posted 16 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The specific aim of this study is to evaluate the safety of non-steroidal anti-inflammatory drugs (NSAIDs) and their impact on renal function and/or contribution to exercise-associated hyponatremia (EAH) during an ultramarathon foot race. There is currently much debate over whether NSAID ingestion during endurance events contributes to acute kidney injury. Endurance events often ignite a "perfect storm" of physiologic insults- heat stress, dehydration, and myopathy- which can all negatively impact kidney function. There is a concern that NSAIDs may further potentiate these negative effects as well as contribute to EAH through its anti-diuretic affect. To date, no powered, prospective study has ever examined the effects of NSAIDs on either of these two biochemical outcomes
Ultramarathon endurance events, defined as any race longer than a marathon (26.2 miles), are increasing in popularity, with a 10% increase in annual participants, and more than 69,000 finishers worldwide in 2013. Considerable literature has documented alterations in serum biochemical profiles of these endurance athletes, with consistent evidence of elevated serum creatinine (Cr) levels in healthy race finishers as well as those seeking medical care. While acute renal failure in ultramarathon runners is a rare occurrence, acute kidney injury is common, ranging from 34% in a single-stage ultramarathon to 55-80% in multi-stage ultramarathons. The evidence is equivocal regarding NSAID ingestion and AKI. One study showed that runners who ingested NSAIDs prior to marathons had greater post-race creatinine levels than matched controls as well as higher rates of hospitalization and acute renal failure. However, this contrasts with several other studies that showed a marked lack of difference in creatinine levels or development of acute kidney injury between NSAID users and non-users during ultramarathons. The only randomized trial to date on this subject found no difference in serum creatinine levels between the NSAID and placebo groups at ultramarathon race end, however conclusions were limited by a small unpowered sample size.
Exercise associated hyponatremia (EAH), defined as a serum sodium concentration below 135mEq/L, is recognized as a relatively common issue in endurance running events. The incidence of EAH varies depending upon the distance of the race, with reported values of 3-28% for marathons, 23 - 38% for triathlons and 4-51% in single-stage ultramarathons. EAH is likely under-diagnosed as athletes are often asymptomatic. While EAH most often manifests as non-specific symptoms such as nausea, vomiting, dizziness, and fatigue, it can be a potentially fatal disease that can progress to encephalopathy, seizures, pulmonary edema, and death. There have been no large prospective studies examining the relationship between EAH and NSAID ingestion.
Detailed description
This study will be conducted during the fifth stage of a 6-stage ultramarathon foot race that covers a total of 250 kilometers. Data will be collected during four separate events over the course of the coming year. All races are run by the RacingThePlanet™ 4-desert race series with locations including: Jordan, Ecuador, China, and Chile. The evening after stage 4, participants will be reminded to check in at the medical tent prior to stage 5 start, and at that time the participants will be weighed and given their study drug packet (ibuprofen or visually identical placebo). Approximately 80% of the finishers complete the 80-kilometer Stage 5 in less than 19 hours, so the majority of participants will ingest 1600mg of ibuprofen (400mg q 4 hours x 4 doses). The optimal adult dosing for analgesia is 400mg every 4 hours, with a maximum daily dose of 3200mg ((1999). Product information: Motrin™, ibuprofen. Kalamazoo, MI, Pharmacia \& Upjohn Company.)
Immediately after crossing the finish line of Stage 5, participants will be reweighed, then seated in the study tent where a fingertip blood sample will be obtained via lancet and capillary collection tube (Mock, Morrison, \& Yatscoff, 1995) then analyzed for Na, Cr and BUN (utilizing a Chem-8 cartridge) onsite immediately after collection using an iSTAT® point-of- care analyzer (Abbott; East Windsor, NJ). Any participant who did not complete any stage prior to stage 5 will be removed from the competition and the study. Both the point-of-care device and the digital scale will be calibrated for prior to taking measurements. At this point, the study is over and there is no further participant responsibilities.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebotasteless and inert tablets |
| Ibuprofen | Active comparator | Drug: IbuprofenEach tablet containing 400mg of ibuprofen |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Any participant in a RacingThePlanet sanctioned event who understands the consent form in English.
Key exclusion criteria (4 listed)
- Allergic to any form of non-steroidal anti-inflammatory
- Taken a NSAID or steroid in prior 12 hours
- 1 kidney
- Known to be pregnant or suspected to be pregnant
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 |
|---|---|---|
| IbuprofenAlso: motrinIbuprofen | Drug | Ibuprofen |
| PlaceboAlso: sugar pillTasteless and inert visually identical (to ibuprofen) pills | Drug | Placebo |
Primary outcome
Acute Kidney Injury
Time frame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours
The participants experiencing acute kidney injury (diagnosed by an increase in creatinine of greater or equal to 1.5x that of estimated baseline creatinine from age and weight) will be from measured point-of-care blood test of the finish line immediately following the completion of a 50 mile ultramarathon. This outcome measure is a biochemical reading, that may not necessarily be a clinical adverse event.
2 secondary outcomes
Perceived Exertion
Time frame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours
Exercise-Associated Hyponatremia
Time frame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28679502Lipman GS, Shea K, Christensen M, Phillips C, Burns P, Higbee R, Koskenoja V, Eifling K, Krabak BJ. Ibuprofen versus placebo effect on acute kidney injury in ultramarathons: a randomised controlled trial. Emerg Med J. 2017 Oct;34(10):637-642. doi: 10.1136/emermed-2016-206353. Epub 2017 Jul 5.
- Individual participant dataSharing planned: No
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Acute Kidney Injury, Hypotension (MeSH: D007022)
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.
Grant S Lipman, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ibuprofen in people with Acute Kidney Injury and Exercise-associated Hyponatremia, run by Stanford University at 1 site in United States.
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 4 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 Dec 2018. 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 United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 (time frame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours). 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 NCT02272725, 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 Dec 2018.