TuberculosisPhase 2NCT01832987
Pharmacokinetic Parameters of Co-trimoxazole
A Phase 2 study testing co-trimoxazole in people with Tuberculosis, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
Rationale: Treatment of multidrug or extensively drug resistant tuberculosis (MDR/XDR-TB) is a real challenge as failure in response to treatment and serious side-effects are frequently encountered. New, more effective drugs with less side effects are therefore urgently needed to solve this problem. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- co-trimoxazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2013to Aug 2014
- 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 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- TB Patients with normal susceptible Mycobacterium tuberculosis
- Patients older than 17 and younger than 64 years.
Who cannot join
- Pregnancy or breast feeding
- Patients with hypersensitivity to sulfonamide or trimethoprim
- Concomitant treatment with vitamin K antagonists (acenocoumarol)
- Patients with preexisting renal dysfunction or concomitant treatment of angiotensin converting enzyme inhibitors and potassium -sparing diuretics) that may exacerbate the hyperkalemic effect of SXT.
- Patients treated with methotrexate, phenytoin, sulfonylureas (glibenclamide, gliclazide, glimepiride en tolbutamide) or procainamide hydrochloride.
- Patients that have gastrointestinal complaints like diarrhea and vomiting (observed)
- Patients that have experienced an adverse effect to SXT or similar antibiotic drugs.
- Patients with HIV or AIDS.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetic Parameters of 960 mg Co-trimoxazole Once Daily in Patients With Tuberculosis
Rationale:
Treatment of multidrug or extensively drug resistant tuberculosis (MDR/XDR-TB) is a real challenge as failure in response to treatment and serious side-effects are frequently encountered. New, more effective drugs with less side effects are therefore urgently needed to solve this problem. Although several new drugs against TB are in the pipeline, physicians currently have limited treatment options for treatment of complicated MDR/XDR-TB cases. Therefore, drugs developed and labeled for other infectious diseases are evaluated for TB. Co-trimoxazole consists of sulfamethoxazole and trimethoprim. Sulfamethoxazole could be effective in the treatment of tuberculosis as shown by Forgacs et al. and Huang et al.
Read more
Furthermore, with dried blood spot (DBS) analysis, the exposure to co-trimoxazole could be analyzed with only some blood drops withdrawn with a finger prick on paper. This paper is suitable for storage, transportation and subsequently analysis without additional cooling or storage requirements.
Objective:
The main objective of this prospective clinical trial is to evaluate pharmacokinetics of 960 mg co-trimoxazole in TB patients. This clinical trial will provide important information on PK of co-trimoxazole in TB patients for future studies.
The second objective is to calculate the T>MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio as efficacy predicting parameter. Furthermore, the analysis of dried blood spots will be clinically validated by comparing results of blood samples withdrawn from venous blood versus withdrawn by finger prick and transferred to filter paper. Retrospectively, data from this study can be used for limited sampling strategies for co-trimoxazole based on a pharmacokinetic population model constructed from the full PK curves of the patients.
Study design:
A prospective pharmacokinetic study.
Study population: 12 TB patients.
Intervention: on 4 to 6 days, 960 mg co-trimoxazole daily will be added to the normal treatment regimen.
Main study parameters/endpoints:
The pharmacokinetic parameters (Vd, Cl, AUC, etc) of co-trimoxazole are the primary endpoints of the study. The T>MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio are most likely the best predictive parameters for efficacy of co-trimoxazole treatment and will be calculated for a range of M tuberculosis isolates.
- Conditions
- Tuberculosis
- Being tested
- co-trimoxazole
- Keywords
- co-trimoxazole, sulfamethoxazole, tuberculosis, pharmacokinetics
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
co-trimoxazoleDrug
Also called Sulfamethoxazole/trimethoprim
On 4, 5 or 6 consecutive days, co-trimoxazole 960 mg will be added to the normal treatment regimen
| Study group | Role | What they receive |
|---|---|---|
| co-trimoxazole | Experimental | On 4, 5 or 6 consecutive days, 960 mg co-trimoxazole (oral) will be added to the normal treatment of tuberculosis. Receives: Drug: co-trimoxazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC
Measuring the AUC over 24 hours of sulfamethoxazole, one out of two compounds of co-trimoxazole after obtaining steady state (960 mg co-trimoxazole).
Measured: 4th, 5th or 6th day
Secondary outcomes (2)
Determination of the AUC/MIC and T>MIC
Determination of the area under the curve divided by the mean inhibitory concentration and the time above MIC.
Measured: 4th, 5th or 6th day
Validating DBS analysis
Validating the analysis of dried blood spots for therapeutic drug monitoring by comparing the concentration measured in venous blood with the concentration measured using the dried blood spot method.
Measured: 4th, 5th or 6th day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2013 (estimated)
- Study startOct 2013
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, JWC Alffenaar, University Medical Center Groningen
- Investigators
- Jan-Willem C Alffenaar, PharmD PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01832987
- Sponsor's protocol ID
- SXT8469
- Status last verified
- Sep 2014
- First submitted
- 11 Apr 2013
- Last updated
- 16 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Alsaad N, van Altena R, Pranger AD, van Soolingen D, de Lange WC, van der Werf TS, Kosterink JG, Alffenaar JW. Evaluation of co-trimoxazole in the treatment of multidrug-resistant tuberculosis. Eur Respir J. 2013 Aug;42(2):504-12. doi: 10.1183/09031936.00114812. Epub 2012 Oct 25.
PubMed 23100498Huang TS, Kunin CM, Yan BS, Chen YS, Lee SS, Syu W Jr. Susceptibility of Mycobacterium tuberculosis to sulfamethoxazole, trimethoprim and their combination over a 12 year period in Taiwan. J Antimicrob Chemother. 2012 Mar;67(3):633-7. doi: 10.1093/jac/dkr501. Epub 2011 Nov 29.
PubMed 22127584Forgacs P, Wengenack NL, Hall L, Zimmerman SK, Silverman ML, Roberts GD. Tuberculosis and trimethoprim-sulfamethoxazole. Antimicrob Agents Chemother. 2009 Nov;53(11):4789-93. doi: 10.1128/AAC.01658-08. Epub 2009 Jun 29.
PubMed 19564358Alsaad N, Dijkstra JA, Akkerman OW, de Lange WC, van Soolingen D, Kosterink JG, van der Werf TS, Alffenaar JW. Pharmacokinetic Evaluation of Sulfamethoxazole at 800 Milligrams Once Daily in the Treatment of Tuberculosis. Antimicrob Agents Chemother. 2016 Jun 20;60(7):3942-7. doi: 10.1128/AAC.02175-15. Print 2016 Jul.
PubMed 27067336
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Parameters of 960 mg Co-trimoxazole Once Daily in Patients With Tuberculosis
- ClinicalTrials.gov ID
- NCT01832987
- Acronym / sponsor ID
- SXT8469
- Conditions
- Tuberculosis
- Keywords
- co-trimoxazole, sulfamethoxazole, tuberculosis, pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 16 Apr 2013 (estimated)
- 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.
Rationale:
Treatment of multidrug or extensively drug resistant tuberculosis (MDR/XDR-TB) is a real challenge as failure in response to treatment and serious side-effects are frequently encountered. New, more effective drugs with less side effects are therefore urgently needed to solve this problem. Although several new drugs against TB are in the pipeline, physicians currently have limited treatment options for treatment of complicated MDR/XDR-TB cases. Therefore, drugs developed and labeled for other infectious diseases are evaluated for TB. Co-trimoxazole consists of sulfamethoxazole and trimethoprim. Sulfamethoxazole could be effective in the treatment of tuberculosis as shown by Forgacs et al. and Huang et al.
Furthermore, with dried blood spot (DBS) analysis, the exposure to co-trimoxazole could be analyzed with only some blood drops withdrawn with a finger prick on paper. This paper is suitable for storage, transportation and subsequently analysis without additional cooling or storage requirements.
Objective:
The main objective of this prospective clinical trial is to evaluate pharmacokinetics of 960 mg co-trimoxazole in TB patients. This clinical trial will provide important information on PK of co-trimoxazole in TB patients for future studies.
The second objective is to calculate the T>MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio as efficacy predicting parameter. Furthermore, the analysis of dried blood spots will be clinically validated by comparing results of blood samples withdrawn from venous blood versus withdrawn by finger prick and transferred to filter paper. Retrospectively, data from this study can be used for limited sampling strategies for co-trimoxazole based on a pharmacokinetic population model constructed from the full PK curves of the patients.
Study design:
A prospective pharmacokinetic study.
Study population: 12 TB patients.
Intervention: on 4 to 6 days, 960 mg co-trimoxazole daily will be added to the normal treatment regimen.
Main study parameters/endpoints:
The pharmacokinetic parameters (Vd, Cl, AUC, etc) of co-trimoxazole are the primary endpoints of the study. The T>MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio are most likely the best predictive parameters for efficacy of co-trimoxazole treatment and will be calculated for a range of M tuberculosis isolates.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| co-trimoxazole | Experimental | Drug: co-trimoxazoleOn 4, 5 or 6 consecutive days, 960 mg co-trimoxazole (oral) will be added to the normal treatment of tuberculosis. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- TB Patients with normal susceptible Mycobacterium tuberculosis
- Patients older than 17 and younger than 64 years.
Key exclusion criteria (8 listed)
- Pregnancy or breast feeding
- Patients with hypersensitivity to sulfonamide or trimethoprim
- Concomitant treatment with vitamin K antagonists (acenocoumarol)
- Patients with preexisting renal dysfunction or concomitant treatment of angiotensin converting enzyme inhibitors and potassium -sparing diuretics) that may exacerbate the hyperkalemic effect of SXT.
- Patients treated with methotrexate, phenytoin, sulfonylureas (glibenclamide, gliclazide, glimepiride en tolbutamide) or procainamide hydrochloride.
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 |
|---|---|---|
| co-trimoxazoleAlso: Sulfamethoxazole/trimethoprimOn 4, 5 or 6 consecutive days, co-trimoxazole 960 mg will be added to the normal treatment regimen | Drug | co-trimoxazole |
Primary outcome
AUC
Time frame: 4th, 5th or 6th day
Measuring the AUC over 24 hours of sulfamethoxazole, one out of two compounds of co-trimoxazole after obtaining steady state (960 mg co-trimoxazole).
2 secondary outcomes
Determination of the AUC/MIC and T>MIC
Time frame: 4th, 5th or 6th day
Validating DBS analysis
Time frame: 4th, 5th or 6th day
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 16 Sep 2014.
- Background: PubMed 23100498Alsaad N, van Altena R, Pranger AD, van Soolingen D, de Lange WC, van der Werf TS, Kosterink JG, Alffenaar JW. Evaluation of co-trimoxazole in the treatment of multidrug-resistant tuberculosis. Eur Respir J. 2013 Aug;42(2):504-12. doi: 10.1183/09031936.00114812. Epub 2012 Oct 25.
- Background: PubMed 22127584Huang TS, Kunin CM, Yan BS, Chen YS, Lee SS, Syu W Jr. Susceptibility of Mycobacterium tuberculosis to sulfamethoxazole, trimethoprim and their combination over a 12 year period in Taiwan. J Antimicrob Chemother. 2012 Mar;67(3):633-7. doi: 10.1093/jac/dkr501. Epub 2011 Nov 29.
- Background: PubMed 19564358Forgacs P, Wengenack NL, Hall L, Zimmerman SK, Silverman ML, Roberts GD. Tuberculosis and trimethoprim-sulfamethoxazole. Antimicrob Agents Chemother. 2009 Nov;53(11):4789-93. doi: 10.1128/AAC.01658-08. Epub 2009 Jun 29.
- Derived from this study: PubMed 27067336Alsaad N, Dijkstra JA, Akkerman OW, de Lange WC, van Soolingen D, Kosterink JG, van der Werf TS, Alffenaar JW. Pharmacokinetic Evaluation of Sulfamethoxazole at 800 Milligrams Once Daily in the Treatment of Tuberculosis. Antimicrob Agents Chemother. 2016 Jun 20;60(7):3942-7. doi: 10.1128/AAC.02175-15. Print 2016 Jul.
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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.
Jan-Willem C Alffenaar, PharmD PhD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing co-trimoxazole in people with Tuberculosis, run by University Medical Center Groningen at 1 site in Netherlands.
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 8 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 16 Sep 2014. 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 Netherlands. 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 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 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?
AUC (time frame: 4th, 5th or 6th day). 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 NCT01832987, which also lists 4 linked publications.
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 16 Sep 2014.