HIV-infected Participants With ESRD Undergoing Routine HemodialysisPhase 4NCT04689737
Removal of Doravirine by Hemodialysis in HIV-Infected Patients With End-stage Renal Disease (ESRD)
A Phase 4 study testing Doravirine in people with HIV-infected Participants With ESRD Undergoing Routine Hemodialysis, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 3 sites in Spain.
Trial summary
Doravirine is a novel non-nucleoside reverse transcriptase inhibitor that has demonstrated good efficacy, tolerability, and safety for the treatment of patients with HIV infection in phase III clinical trials. Doravirine achieved non- inferiority when compared with efavirenz- and darunavir/ritonavir-based regimens. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- HIV-infected Participants With ESRD Undergoing Routine Hemodialysis
- What is being tested?
- Doravirine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 3 sitesSpain
- Study dates
- 20 Mar 2021to 14 Jun 2021
- Phase
- Phase 4
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females* aging ≥ 18 years.
- Documented HIV infection).
- Stable antiretroviral treatment for at least 2 weeks prior to enrolment.
- Optimal adherence to antiretroviral treatment, defined as less than 2 missed doses within the previousweek.
- End-stage renal disease in renal replacement therapy with periodic hemodialysis.
- Agree with the study procedures and signature of the informed consent. *Women of childbearing potential must have a negative pregnancy test prior to randomization into the study and commitment to useat least one of these birth control methods: male or female condom with or without spermicide, cap, diaphragm or sponge with orwithout spermicide, intrauterine device, bilateral tubal occlusion, vasectomized partner, sexual abstinence during the study. Condomuse is considered as an additional method of contraception only and cannot be the only method of contraception used as not beenconsidered an effective method by the Clinical Trial Facilitation Group (CTFG) guidelines.
- Based on ICH, M3 (R2) 2009 a woman is considered of childbearing potential: fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include tubal ligation, hysterectomy, bilateral oophorectomy.
Who cannot join
- Evidence or clinical suspicion that the patient will not be able to comply with the study protocol.
- Hypersensitivity to doravirine
- Concomitant therapy within the previous 4 weeks with any of the following drugs:
- Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin
- Androgen receptor inhibitor: enzalutamide
- Antimycobacterials: rifampin, rifapentine
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- Cytotoxic agent: mitotane
- St. John's wort (Hypericum perforatum)
- Females who are pregnant or breastfeeding.
- ALT and/ or AST ≥ 4 times the upper limit of normal (ULN) at screening.
- Hemoglobin < 7,5 g/dL at screening.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Germans Trias i Pujol Hospital
Badalona, Barcelona, 08916
Valle Hebron Hospital
Barcelona, 08035
Universitario Bellvitge Hospital
L'Hospitalet de Llobregat, Barcelona, 08907
About this study
Official title: Removal of Doravirine by Hemodialysis in HIV-Infected Patients With End-Stage Renal Disease (ESRD)
Doravirine is a novel non-nucleoside reverse transcriptase inhibitor that has demonstrated good efficacy, tolerability, and safety for the treatment of patients with HIV infection in phase III clinical trials. Doravirine achieved non- inferiority when compared with efavirenz- and darunavir/ritonavir-based regimens. Doravirine is mainly metabolized and eliminated by the liver, with only 6% of the drug being excreted unchanged through the urine.In a study comparing 8 subjects with severe renal disease to 8 subjects without renal impairment, the single dose exposure of doravirine was 43% higher in subjects with severe renal function impairment.However, according to prescribing information, no dosage adjustment of doravirine is required in patients with mild, moderate, or severe renal impairment. On the other hand, data on doravirine pharmacokinetics in patients with ESRD on dialysis are lacking. This may be of special interest because doravirine has a relatively low molecular weight and it is only 76% bound to proteins in plasma. These characteristics could make possible for hemodialysis to remove doravirine from plasma, potentially leading to subtherapeutic concentrations of doravirine after the dialysis sessions. On the contrary, doravirine volume of distribution is about 60 liters,15 what could limit extraction of doravirine by hemodialysis. Since data on doravirine pharmacokinetics in PLWH with ESRD on dialysis are lacking, our aim is to evaluate the effect of intermittent hemodialysis on doravirine concentrations in HIV-infected patients with ESRD
Read the detailed description
Doravirine is a novel non-nucleoside reverse transcriptase inhibitor that has demonstrated good efficacy, tolerability, and safety for the treatment of patients with HIV infection in phase III clinical trials. Doravirine achieved non- inferiority when compared with efavirenz- and darunavir/ritonavir-based regimens. Doravirine is mainly metabolized and eliminated by the liver, with only 6% of the drug being excreted unchanged through the urine.In a study comparing 8 subjects with severe renal disease to 8 subjects without renal impairment, the single dose exposure of doravirine was 43% higher in subjects with severe renal function impairment.However, according to prescribing information, no dosage adjustment of doravirine is required in patients with mild, moderate, or severe renal impairment. On the other hand, data on doravirine pharmacokinetics in patients with ESRD on dialysis are lacking. This may be of special interest because doravirine has a relatively low molecular weight and it is only 76% bound to proteins in plasma. These characteristics could make possible for hemodialysis to remove doravirine from plasma, potentially leading to subtherapeutic concentrations of doravirine after the dialysis sessions. On the contrary, doravirine volume of distribution is about 60 liters,15 what could limit extraction of doravirine by hemodialysis. Since data on doravirine pharmacokinetics in PLWH with ESRD on dialysis are lacking, our aim is to evaluate the effect of intermittent hemodialysis on doravirine concentrations in HIV-infected patients with ESRD.
- Being tested
- Doravirine
- Keywords
- HIV, ESRD, Doravirine
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoravirineDrug
Also called Pifeltro
Participants will be told to take one tablet of doravirine (Pifeltro, MDS) once daily, with or without food, approximately at the day time that they usually finish the hemodialysis sessions. The rest of their antiretroviral regimen and concomitant medications will remain unchanged
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Doravirine (Pifeltro, MSD) will be added to participant's cART (100 mg once daily) for 5 days Receives: Drug: Doravirine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentatge of Doravirine Dialysis Extraction Ratio (ER)
The haemodialysis extraction ratio (ER) for doravirine was calculated as: ER(%) = ((Cin - Cout)/ Cin) × 100 where Cin is the pre-dialyser doravirine concentration (i.e. blood entering the dialyser) and Cout is the post-dialyser doravirine concentration (i.e. blood leaving the dialyser). Post-dialyser doravirine concentrations (Cout) were corrected for haemoconcentration by a factor F based on total protein (TP) concentration pre- and post-dialyser: F = TPin / TPout.
Measured: At day 6
Secondary outcomes (2)
Percentage of Participants Developing Related Adverse Events Grade 3-4 Related to Doravirine
Percentage of participants developing related adverse events grade 3 or grade 4 related to doravirine. Defining Grade 3 (severe) as symptoms causing inability to perform usual social and functional activities and Grade 4 (potentially life-threatening)as Symptoms causing inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.
Measured: Baseline to day 20
Doravirine Concentration (mg/dl)
Doravirine Concentration (mg/dl) in plasma at the end of the haemodialysis session.
Measured: At day 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2020
- Study start20 Mar 2021
- Primary completion14 Jun 2021
- Study completion14 Jun 2021
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 HIV-infected Participants With ESRD Undergoing Routine HemodialysisStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- This is a multi-centre, single-arm, open-label, pilot study in HIV-infected participants with ESRD undergoing routine hemodialysis. All participants will receive doravirine 100 mg once daily during the study (5 days).
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04689737
- Sponsor's protocol ID
- Dora-HD
- Status last verified
- Aug 2023
- First submitted
- 29 Dec 2020
- Last updated
- 27 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Molto J, Graterol F, Curran A, Ramos N, Imaz A, Sandoval D, Perez F, Bailon L, Khoo S, Else L, Paredes R. Removal of doravirine by haemodialysis in people living with HIV with end-stage renal disease. J Antimicrob Chemother. 2022 Jun 29;77(7):1989-1991. doi: 10.1093/jac/dkac126.
PubMed 35425985
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Removal of Doravirine by Hemodialysis in HIV-Infected Patients With End-Stage Renal Disease (ESRD)
- ClinicalTrials.gov ID
- NCT04689737
- Acronym / sponsor ID
- Dora-HD
- Keywords
- HIV, ESRD, Doravirine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la CienciaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 20 Mar 2021 (actual)
- Primary completion
- 14 Jun 2021 (actual)
- Study completion
- 14 Jun 2021 (actual)
- First posted
- 30 Dec 2020 (actual)
- Results
- Posted 27 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Doravirine is a novel non-nucleoside reverse transcriptase inhibitor that has demonstrated good efficacy, tolerability, and safety for the treatment of patients with HIV infection in phase III clinical trials. Doravirine achieved non- inferiority when compared with efavirenz- and darunavir/ritonavir-based regimens. Doravirine is mainly metabolized and eliminated by the liver, with only 6% of the drug being excreted unchanged through the urine.In a study comparing 8 subjects with severe renal disease to 8 subjects without renal impairment, the single dose exposure of doravirine was 43% higher in subjects with severe renal function impairment.However, according to prescribing information, no dosage adjustment of doravirine is required in patients with mild, moderate, or severe renal impairment. On the other hand, data on doravirine pharmacokinetics in patients with ESRD on dialysis are lacking. This may be of special interest because doravirine has a relatively low molecular weight and it is only 76% bound to proteins in plasma. These characteristics could make possible for hemodialysis to remove doravirine from plasma, potentially leading to subtherapeutic concentrations of doravirine after the dialysis sessions. On the contrary, doravirine volume of distribution is about 60 liters,15 what could limit extraction of doravirine by hemodialysis. Since data on doravirine pharmacokinetics in PLWH with ESRD on dialysis are lacking, our aim is to evaluate the effect of intermittent hemodialysis on doravirine concentrations in HIV-infected patients with ESRD
Detailed description
Doravirine is a novel non-nucleoside reverse transcriptase inhibitor that has demonstrated good efficacy, tolerability, and safety for the treatment of patients with HIV infection in phase III clinical trials. Doravirine achieved non- inferiority when compared with efavirenz- and darunavir/ritonavir-based regimens. Doravirine is mainly metabolized and eliminated by the liver, with only 6% of the drug being excreted unchanged through the urine.In a study comparing 8 subjects with severe renal disease to 8 subjects without renal impairment, the single dose exposure of doravirine was 43% higher in subjects with severe renal function impairment.However, according to prescribing information, no dosage adjustment of doravirine is required in patients with mild, moderate, or severe renal impairment. On the other hand, data on doravirine pharmacokinetics in patients with ESRD on dialysis are lacking. This may be of special interest because doravirine has a relatively low molecular weight and it is only 76% bound to proteins in plasma. These characteristics could make possible for hemodialysis to remove doravirine from plasma, potentially leading to subtherapeutic concentrations of doravirine after the dialysis sessions. On the contrary, doravirine volume of distribution is about 60 liters,15 what could limit extraction of doravirine by hemodialysis. Since data on doravirine pharmacokinetics in PLWH with ESRD on dialysis are lacking, our aim is to evaluate the effect of intermittent hemodialysis on doravirine concentrations in HIV-infected patients with ESRD.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a multi-centre, single-arm, open-label, pilot study in HIV-infected participants with ESRD undergoing routine hemodialysis. All participants will receive doravirine 100 mg once daily during the study (5 days).
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: DoravirineDoravirine (Pifeltro, MSD) will be added to participant's cART (100 mg once daily) for 5 days |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Males and females* aging ≥ 18 years.
- Documented HIV infection).
- Stable antiretroviral treatment for at least 2 weeks prior to enrolment.
- Optimal adherence to antiretroviral treatment, defined as less than 2 missed doses within the previousweek.
- End-stage renal disease in renal replacement therapy with periodic hemodialysis.
Key exclusion criteria (11 listed)
- Evidence or clinical suspicion that the patient will not be able to comply with the study protocol.
- Hypersensitivity to doravirine
- Concomitant therapy within the previous 4 weeks with any of the following drugs:
- Females who are pregnant or breastfeeding.
- ALT and/ or AST ≥ 4 times the upper limit of normal (ULN) at screening.
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 |
|---|---|---|
| DoravirineAlso: PifeltroParticipants will be told to take one tablet of doravirine (Pifeltro, MDS) once daily, with or without food, approximately at the day time that they usually finish the hemodialysis sessions. The rest of their antiretroviral regimen and concomitant medications will remain unchanged | Drug | Experimental group |
Primary outcome
Percentatge of Doravirine Dialysis Extraction Ratio (ER)
Time frame: At day 6
The haemodialysis extraction ratio (ER) for doravirine was calculated as: ER(%) = ((Cin - Cout)/ Cin) × 100 where Cin is the pre-dialyser doravirine concentration (i.e. blood entering the dialyser) and Cout is the post-dialyser doravirine concentration (i.e. blood leaving the dialyser). Post-dialyser doravirine concentrations (Cout) were corrected for haemoconcentration by a factor F based on total protein (TP) concentration pre- and post-dialyser: F = TPin / TPout.
2 secondary outcomes
Percentage of Participants Developing Related Adverse Events Grade 3-4 Related to Doravirine
Time frame: Baseline to day 20
Doravirine Concentration (mg/dl)
Time frame: At day 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35425985Molto J, Graterol F, Curran A, Ramos N, Imaz A, Sandoval D, Perez F, Bailon L, Khoo S, Else L, Paredes R. Removal of doravirine by haemodialysis in people living with HIV with end-stage renal disease. J Antimicrob Chemother. 2022 Jun 29;77(7):1989-1991. doi: 10.1093/jac/dkac126.
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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Doravirine in people with HIV-infected Participants With ESRD Undergoing Routine Hemodialysis, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 3 sites in Spain.
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 7 inclusion and 11 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 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. 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?
Yes. Results are posted in the registry (first posted 27 Aug 2024). 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?
Percentatge of Doravirine Dialysis Extraction Ratio (ER) (time frame: At day 6). 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 NCT04689737, 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 27 Aug 2024.