Pneumonia, Pneumocystis CariniiPhase 2NCT00000655
A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients
A Phase 2 study testing Atovaquone and Sulfamethoxazole-Trimethoprim in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 38 sites in 8 countries.
Trial summary
To evaluate the effectiveness of atovaquone (566C80) compared to a standard antipneumocystis agent, (SMX/TMP), for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Pneumonia, Pneumocystis Carinii, HIV Infections
- What is being tested?
- Atovaquone and Sulfamethoxazole-Trimethoprim
- How many people
- 300 participants
- Where
- 38 sitesin 8 countries
- Study dates
- Start not givento Jan 1992
- 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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient must have the following:
- Presumptive diagnosis of AIDS as defined by the CDC.
- Untreated Pneumocystis carinii pneumonia (PCP).
- Willingness and ability to give informed consent.
- Prior Medication:
- Allowed:
- Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) including aerosolized pentamidine or sulfamethoxazole/trimethoprim (SMX/TMP) (at a dose no greater than two DS tablets twice daily).
Who cannot join
- Co-existing Condition:
- Patients with the following conditions or symptoms are excluded:
- Judged by the investigator to be in impending respiratory failure.
- Malabsorption or vomiting that would, in the judgment of investigator, potentially limit the retention and absorption of an oral therapy.
- Concurrent bacterial, fungal, or viral pneumonitis, pulmonary Kaposi's sarcoma or other concurrent illness, or chronic pulmonary disease that, in the investigator's opinion, would make interpretation of drug efficacy difficult.
- Concurrent Medication:
Show all 32Show fewer
- Excluded:
- Corticosteroid treatment (except replacement therapy or patients in Group B).
- Ganciclovir.
- Zidovudine (AZT).
- Investigational agents including antiretroviral agents (didanosine (ddI), dideoxycytidine (ddC), etc.).
- Drugs likely to have anti-pneumocystis effect such as:
- Sulfonamides.
- Pentamidine.
- Dapsone.
- Trimethoprim.
- Other DHFR inhibitors.
- Primaquine.
- Clindamycin.
- Sulfonylureas.
- Patients with the following are excluded:
- Judged by the investigator to be in impending respiratory failure.
- Prior therapy for this episode of PCP or treatment within 4 weeks of entry for a prior episode of PCP.
- Unable to or refuse to discontinue zidovudine, ganciclovir, or other antiretroviral agents during the 21 day treatment period.
- Unable to take medication orally or unwilling or unable to take study medication with food.
- Significant psychosis or emotional disorder such that, in the investigator's opinion, the patient would not be compliant with the study protocol.
- Prior documented glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Prior history of life-threatening toxicity to SMX/TMP such as severe rash or Stevens-Johnson syndrome.
- Prior Medication:
- Excluded:
- Prior therapy for this episode of Pneumocystis carinii pneumonia (PCP) or treatment within 4 weeks for a prior episode of PCP.
- Blood transfusions.
Trial locations and contacts
38 sites in 8 countries.
38 sites in 8 countries
United States27 sites
Johns Hopkins Univ School of Medicine
Baltimore, Maryland, 21205
Natl Inst of Allergy & Infect Dis / Cln Ctr
Bethesda, Maryland, 20892
Univ of Alabama at Birmingham
Birmingham, Alabama, 35294
Univ of Cincinnati
Cincinnati, Ohio, 452670405
Duke Univ Med Ctr
Durham, North Carolina, 27710
Kaiser Foundation Hosp
Harbor City, California, 90710
Plaza Med Ctr
Houston, Texas, 77004
Baylor College of Medicine
Houston, Texas, 77030
USC
Los Angeles, California, 90033
Dr Richard Meyer
Los Angeles, California, 90048
UCLA CARE Ctr
Los Angeles, California, 90095
Regional Med Ctr at Memphis
Memphis, Tennessee, 38103
The Regional Medical Ctr, Memphis
Memphis, Tennessee, 38105
Beth Israel Med Ctr / Peter Krueger Clinic
New York, New York, 10003
Saint Vincent's Hosp and Med Ctr
New York, New York, 10011
Harlem AIDS Treatment Group / Harlem Hosp Ctr
New York, New York, 10037
Infectious Disease Med Group
Oakland, California, 94609
Buckley Braffman Stern Med Associates
Philadelphia, Pennsylvania, 19107
Good Samaritan Hosp
Portland, Oregon, 972103079
Dr Winkler Weinberg
Roswell, Georgia, 30076
Univ of California / San Diego Treatment Ctr
San Diego, California, 921036325
San Francisco Gen Hosp
San Francisco, California, 941102859
UCSF - San Francisco Gen Hosp
San Francisco, California, 94110
Dr Marcus Conant
San Francisco, California, 94115
Washington Univ School of Medicine
St Louis, Missouri, 63108
Georgetown Univ Med Ctr
Washington D.C., District of Columbia, 20007
Veterans Administration Med Ctr
Washington D.C., District of Columbia, 20422
Canada3 sites
Montreal Gen Hosp
Montreal, Quebec
Wellesley Hosp
Toronto, Ontario
Dr Julio S G Montaner
Vancouver, British Columbia
Germany2 sites
August-Viktoria-Krankenhaus Chefarst derII Inneren Abteilung
Berlin
Universitat Munchen / Medizinische Poliklinik
Munich
United Kingdom2 sites
Kobler Centre / Saint Stephen's Hosp
London
Saint Mary's Hosp
London
Puerto Rico1 site
San Juan Veterans Administration Med Ctr
San Juan, 009275800
About this study
Official title: A Randomized, Double-Blind Study of 566C80 Versus Septra (Trimethoprim/Sulfamethoxazole) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients
To evaluate the effectiveness of atovaquone (566C80) compared to a standard antipneumocystis agent, (SMX/TMP), for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients. To compare the safety of short-term (21 days) treatment with 566C80 and SMX/TMP in AIDS patients with an acute episode of PCP.
Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.
Read the detailed description
Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.
Patients are randomized into one of two treatment groups to receive either (1) 566C80 for 21 days, or (2) SMX/TMP for 21 days. Patients will be stratified according to severity of PCP. Group A will be those with an arterial-alveolar (A-a) DO2 < 35 mm Hg. Group B will have an A-a DO2 of 35-45 mm Hg., and will also be required to receive therapy with Corticosteroids. All doses are taken with food. During the 21 days of treatment, patients are examined clinically for adverse effects and have hematology (blood-related) and clinical chemistry studies conducted a minimum of 2 times weekly. More frequent monitoring may be required at the discretion of the investigator. To evaluate the effectiveness of study medication, the clinical status of each patient is evaluated 2 to 3 times per week (e.g., dyspnea score, cough score, chest tightness/pain score, vital signs). Also, on days 7 and 21 of treatment, an arterial blood gas measurement and chest X-ray are performed. Patients who experience severe toxicities will be discontinued from the study and placed on alternative therapy. Patients will also be removed from study if they show significant clinical deterioration within the first 7 days of therapy or if there is no improvement after 10 days of therapy. This study involves a double placebo with one group randomized to receive oral 566C80 and placebo tablets which look like SMX/TMP while the other group will receive SMX/TMP and placebo tablets looking like 566C80.
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Being tested
- Atovaquone, Sulfamethoxazole-Trimethoprim
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Naphthoquinones, Antifungal Agents, Acquired Immunodeficiency Syndrome, Sulfamethoxazole-Trimethoprim
- Medical subject headings
- Pneumonia, Pneumocystis, HIV Infections, AIDS-Related Opportunistic Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtovaquoneDrug
Sulfamethoxazole-TrimethoprimDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Primary completionJan 1992
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pneumonia, Pneumocystis CariniiStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Intervention model
- Parallel groups
- Enrolment
- 300 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Glaxo Wellcome
- Investigators
- Hughes WT, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000655
- Sponsor's protocol ID
- ACTG 167
- Other IDs
- NIAID 90-CC-185, Protocol #03, FDA 53A, Project P71
- Status last verified
- Feb 2011
- First submitted
- 2 Nov 1999
- Last updated
- 1 Mar 2011
- Results posted
- No
Publications
Hughes W, et al. Comparison of 566C80 & trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of P. carinii pneumonitis (PCP). An International Multicenter, CCTG & ACTG Collaboration. Int Conf AIDS. 1992 Jul 19-24;8(1):We48 (abstract no WeB 1019)
Hughes W, Leoung G, Kramer F, Bozzette SA, Safrin S, Frame P, Clumeck N, Masur H, Lancaster D, Chan C, et al. Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med. 1993 May 27;328(21):1521-7. doi: 10.1056/NEJM199305273282103.
PubMed 8479489
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind Study of 566C80 Versus Septra (Trimethoprim/Sulfamethoxazole) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients
- ClinicalTrials.gov ID
- NCT00000655
- Acronym / sponsor ID
- ACTG 167
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Naphthoquinones, Antifungal Agents, Acquired Immunodeficiency Syndrome, Sulfamethoxazole-Trimethoprim
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Glaxo Wellcome
- Primary completion
- Jan 1992 (actual)
- First posted
- 31 Aug 2001 (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.
To evaluate the effectiveness of atovaquone (566C80) compared to a standard antipneumocystis agent, (SMX/TMP), for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients. To compare the safety of short-term (21 days) treatment with 566C80 and SMX/TMP in AIDS patients with an acute episode of PCP.
Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.
Detailed description
Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.
Patients are randomized into one of two treatment groups to receive either (1) 566C80 for 21 days, or (2) SMX/TMP for 21 days. Patients will be stratified according to severity of PCP. Group A will be those with an arterial-alveolar (A-a) DO2 < 35 mm Hg. Group B will have an A-a DO2 of 35-45 mm Hg., and will also be required to receive therapy with Corticosteroids. All doses are taken with food. During the 21 days of treatment, patients are examined clinically for adverse effects and have hematology (blood-related) and clinical chemistry studies conducted a minimum of 2 times weekly. More frequent monitoring may be required at the discretion of the investigator. To evaluate the effectiveness of study medication, the clinical status of each patient is evaluated 2 to 3 times per week (e.g., dyspnea score, cough score, chest tightness/pain score, vital signs). Also, on days 7 and 21 of treatment, an arterial blood gas measurement and chest X-ray are performed. Patients who experience severe toxicities will be discontinued from the study and placed on alternative therapy. Patients will also be removed from study if they show significant clinical deterioration within the first 7 days of therapy or if there is no improvement after 10 days of therapy. This study involves a double placebo with one group randomized to receive oral 566C80 and placebo tablets which look like SMX/TMP while the other group will receive SMX/TMP and placebo tablets looking like 566C80.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Presumptive diagnosis of AIDS as defined by the CDC.
- Untreated Pneumocystis carinii pneumonia (PCP).
- Willingness and ability to give informed consent.
- Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) including aerosolized pentamidine or sulfamethoxazole/trimethoprim (SMX/TMP) (at a dose no greater than two DS tablets twice daily).
Key exclusion criteria (32 listed)
- Judged by the investigator to be in impending respiratory failure.
- Malabsorption or vomiting that would, in the judgment of investigator, potentially limit the retention and absorption of an oral therapy.
- Concurrent bacterial, fungal, or viral pneumonitis, pulmonary Kaposi's sarcoma or other concurrent illness, or chronic pulmonary disease that, in the investigator's opinion, would make interpretation of drug efficacy difficult.
- Corticosteroid treatment (except replacement therapy or patients in Group B).
- Ganciclovir.
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 |
|---|---|---|
| Atovaquone | Drug | – |
| Sulfamethoxazole-Trimethoprim | Drug | – |
Primary outcome
Not reported in the source record.
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 1 Mar 2011.
- BackgroundHughes W, et al. Comparison of 566C80 & trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of P. carinii pneumonitis (PCP). An International Multicenter, CCTG & ACTG Collaboration. Int Conf AIDS. 1992 Jul 19-24;8(1):We48 (abstract no WeB 1019)
- Background: PubMed 8479489Hughes W, Leoung G, Kramer F, Bozzette SA, Safrin S, Frame P, Clumeck N, Masur H, Lancaster D, Chan C, et al. Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med. 1993 May 27;328(21):1521-7. doi: 10.1056/NEJM199305273282103.
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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.
Hughes WT study chair
38 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atovaquone and Sulfamethoxazole-Trimethoprim in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 38 sites in 8 countries.
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 32 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 1 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Canada, Germany, United Kingdom, Belgium and 3 more countries. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000655, which also lists 2 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 1 Mar 2011.